Lee NH

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Full name : Lee Norman H

First name : Norman H

Mail : Department of Pharmacology and Physiology, George Washington University, Washington, DC

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Country : USA

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References (30)

Title : Terrein reduces age-related inflammation induced by oxidative stress through Nrf2\/ERK1\/2\/HO-1 signalling in aged HDF cells - Lee_2015_Cell.Biochem.Funct_33_479
Author(s) : Lee YH , Lee SJ , Jung JE , Kim JS , Lee NH , Yi HK
Ref : Cell Biochemistry & Function , 33 :479 , 2015
Abstract : This study investigated whether multiple bioactivity of terrein such as anti-inflammatory and anti-oxidant inhibits age-related inflammation by promoting an antioxidant response in aged human diploid fibroblast (HDF) cells. HDF cells were cultured serially for in vitro replicative senescence. To create the ageing cell phenotype, intermediate stage (PD31) HDF cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide (H2 O2). Terrein increased cell viability even with H2O2 stress and reduced inflammatory molecules such as intracellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). Terrein reduced also phospho-extracellular kinase receptor1/2 (p-EKR1/2) signalling in aged HDF cells. SIPS cells were attenuated for age-related biological markers including reactive oxygen species (ROS), senescence associated beta-galactosidase (SA beta-gal.) and the aforementioned inflammatory molecules. Terrein induced the induction of anti-oxidant molecules, copper/zinc-superoxide defence (Cu/ZnSOD), manganese superoxide dismutase (MnSOD) and heme oxygenase-1 (HO-1) in SIPS cells. Terrein also alleviated reactive oxygen species formation through the Nrf2/HO-1/p-ERK1/2 pathway in aged cells. The results indicate that terrein has an alleviative function of age-related inflammation characterized as an anti-oxidant. Terrein might be a useful nutraceutical compound for anti-ageing.
ESTHER : Lee_2015_Cell.Biochem.Funct_33_479
PubMedSearch : Lee_2015_Cell.Biochem.Funct_33_479
PubMedID: 26416516
Gene_locus related to this paper: aspte-AT1

Title : Enhancement of osteoblast biocompatibility on titanium surface with Terrein treatment - Lee_2010_Cell.Biochem.Funct_28_678
Author(s) : Lee YH , Lee NH , Bhattarai G , Oh YT , Yu MK , Yoo ID , Jhee EC , Yi HK
Ref : Cell Biochemistry & Function , 28 :678 , 2010
Abstract : Titanium is biocompatible with bodily tissues. However, the formation of ROS on the titanium surfaces might have negative response of the activity of the surroundings cells. Terrein was isolated from Penicullium sp. 20135 and found to reduce the effects of LPS-induced inflammation. This study examined the role of Terrein on the biocompatibility of titanium to determine if it can help improve osseointegration. MC-3T3 E1 cells were grown on titanium surfaces. The biocompatibility of Terrein was examined by adding it directly to the culture media at the indicated concentration. The cells on the titanium surface produced excessive ROS and decreased the activity of Cu/Zn SOD and Mn SOD. Moreover, the cells had higher activity towards oxidative stress molecules, such as MAPK, FAK and iNOS expression. In addition, MC-3T3 E1 osteoblast-like cells promoted osteoclast differentiation but reduced osteoblast differentiation and mineralization on the titanium surface. Interestingly, the cells given the Terrein treatment showed higher resistance towards oxidative stress through the up-regulation of ERK1/2 and FAK activity but the down-regulation of SAPK/JNK and iNOS activity. Moreover, Terrein promoted osteoblast differentiation and bone mineralization to elevate the activity of ALP, SPARC and down-regulate RANKL expression after blocking NF-kappaB translocation from the cytosol to the nucleus. In conclusion, the presence of Terrein on titanium surfaces increases osteoblast cell growth without inflammation. Moreover, Terrein, as a putative antioxidant agent, may enhance osseointegration by decreasing the level of ROS and having a potentially synergistic effect on osteoblast differentiation.
ESTHER : Lee_2010_Cell.Biochem.Funct_28_678
PubMedSearch : Lee_2010_Cell.Biochem.Funct_28_678
PubMedID: 21104936
Gene_locus related to this paper: aspte-AT1

Title : Persistent gene expression changes in ventral tegmental area of adolescent but not adult rats in response to chronic nicotine - Doura_2010_Neurosci_170_503
Author(s) : Doura MB , Luu TV , Lee NH , Perry DC
Ref : Neuroscience , 170 :503 , 2010
Abstract : Because adolescent brains are undergoing extensive developmental changes, they may be uniquely sensitive to effects of addictive drugs like nicotine. We exposed adolescent and adult rats to nicotine infusion for two weeks, and then used whole genome microarray analysis to determine effects on gene expression in the ventral tegmental area. We examined brains immediately after two weeks of nicotine or saline, and also four weeks after termination of nicotine exposure. After identifying genes with a significant agextreatment interaction, we employed template matching to find specific patterns of expression across age and treatment. Of those genes that were transiently regulated (up- or down-regulated immediately following the end of nicotine treatment, but back to saline baseline 30 days later), two-thirds were specific to adult animals, while only 30% were specific to adolescents and 4% were shared across the two ages. In contrast, significant genes that were persistently regulated (altered following nicotine treatment and still altered 30 days later) were more likely (59%) to be adolescent, with only 32% in adults and 8% shared. The greatest number of significant genes was late-regulated (no change immediately after nicotine, but regulated 30 days later). Again, most were in adolescents (54%), compared to adults (10%) or shared (36%). Pathway analysis revealed that adolescent-specific genes were over-represented in several biological functions and canonical pathways, including nervous system development and function and long-term potentiation. Furthermore, adolescent-specific genes formed extensive interaction networks, unlike those specific for adults or shared. This age-specific expression pattern may relate to the heightened vulnerability of adolescents to the effects of addictive drugs. In particular, the propensity of adolescents to show persistent alterations in gene expression corresponds to the persistence of drug dependence among smokers who began their habit as adolescents. These findings support a model whereby adolescent brains are uniquely vulnerable to long-term changes in gene expression in the brain's reward pathway caused by early exposure to nicotine.
ESTHER : Doura_2010_Neurosci_170_503
PubMedSearch : Doura_2010_Neurosci_170_503
PubMedID: 20633606

Title : Poster: Chronic nicotine exposure differentially alters gene expression in VTA from adolescent and adult rats -
Author(s) : Doura MB , Lee NH , Perry DC
Ref : Biochemical Pharmacology , 78 :914 , 2009
PubMedID:

Title : Genome sequence of Aedes aegypti, a major arbovirus vector - Nene_2007_Science_316_1718
Author(s) : Nene V , Wortman JR , Lawson D , Haas B , Kodira C , Tu ZJ , Loftus B , Xi Z , Megy K , Grabherr M , Ren Q , Zdobnov EM , Lobo NF , Campbell KS , Brown SE , Bonaldo MF , Zhu J , Sinkins SP , Hogenkamp DG , Amedeo P , Arensburger P , Atkinson PW , Bidwell S , Biedler J , Birney E , Bruggner RV , Costas J , Coy MR , Crabtree J , Crawford M , Debruyn B , Decaprio D , Eiglmeier K , Eisenstadt E , El-Dorry H , Gelbart WM , Gomes SL , Hammond M , Hannick LI , Hogan JR , Holmes MH , Jaffe D , Johnston JS , Kennedy RC , Koo H , Kravitz S , Kriventseva EV , Kulp D , LaButti K , Lee E , Li S , Lovin DD , Mao C , Mauceli E , Menck CF , Miller JR , Montgomery P , Mori A , Nascimento AL , Naveira HF , Nusbaum C , O'Leary S , Orvis J , Pertea M , Quesneville H , Reidenbach KR , Rogers YH , Roth CW , Schneider JR , Schatz M , Shumway M , Stanke M , Stinson EO , Tubio JM , Vanzee JP , Verjovski-Almeida S , Werner D , White O , Wyder S , Zeng Q , Zhao Q , Zhao Y , Hill CA , Raikhel AS , Soares MB , Knudson DL , Lee NH , Galagan J , Salzberg SL , Paulsen IT , Dimopoulos G , Collins FH , Birren B , Fraser-Liggett CM , Severson DW
Ref : Science , 316 :1718 , 2007
Abstract : We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
ESTHER : Nene_2007_Science_316_1718
PubMedSearch : Nene_2007_Science_316_1718
PubMedID: 17510324
Gene_locus related to this paper: aedae-ACHE , aedae-ACHE1 , aedae-glita , aedae-q0iea6 , aedae-q0iev6 , aedae-q0ifn6 , aedae-q0ifn8 , aedae-q0ifn9 , aedae-q0ifp0 , aedae-q0ig41 , aedae-q1dgl0 , aedae-q1dh03 , aedae-q1dh19 , aedae-q1hqe6 , aedae-Q8ITU8 , aedae-Q8MMJ6 , aedae-Q8T9V6 , aedae-q16e91 , aedae-q16f04 , aedae-q16f25 , aedae-q16f26 , aedae-q16f28 , aedae-q16f29 , aedae-q16f30 , aedae-q16gq5 , aedae-q16iq5 , aedae-q16je0 , aedae-q16je1 , aedae-q16je2 , aedae-q16ks8 , aedae-q16lf2 , aedae-q16lv6 , aedae-q16m61 , aedae-q16mc1 , aedae-q16mc6 , aedae-q16mc7 , aedae-q16md1 , aedae-q16ms7 , aedae-q16nk5 , aedae-q16rl5 , aedae-q16rz9 , aedae-q16si8 , aedae-q16t49 , aedae-q16wf1 , aedae-q16x18 , aedae-q16xp8 , aedae-q16xu6 , aedae-q16xw5 , aedae-q16xw6 , aedae-q16y04 , aedae-q16y05 , aedae-q16y06 , aedae-q16y07 , aedae-q16y39 , aedae-q16y40 , aedae-q16yg4 , aedae-q16z03 , aedae-q17aa7 , aedae-q17av1 , aedae-q17av2 , aedae-q17av3 , aedae-q17av4 , aedae-q17b28 , aedae-q17b29 , aedae-q17b30 , aedae-q17b31 , aedae-q17b32 , aedae-q17bm3 , aedae-q17bm4 , aedae-q17bv7 , aedae-q17c44 , aedae-q17cz1 , aedae-q17d32 , aedae-q17g39 , aedae-q17g40 , aedae-q17g41 , aedae-q17g42 , aedae-q17g43 , aedae-q17g44 , aedae-q17gb8 , aedae-q17gr3 , aedae-q17if7 , aedae-q17if9 , aedae-q17ig1 , aedae-q17ig2 , aedae-q17is4 , aedae-q17l09 , aedae-q17m26 , aedae-q17mg9 , aedae-q17mv4 , aedae-q17mv5 , aedae-q17mv6 , aedae-q17mv7 , aedae-q17mw8 , aedae-q17mw9 , aedae-q17nw5 , aedae-q17nx5 , aedae-q17pa4 , aedae-q17q69 , aedae-q170k7 , aedae-q171y4 , aedae-q172e0 , aedae-q176i8 , aedae-q176j0 , aedae-q177k1 , aedae-q177k2 , aedae-q177l9 , aedae-j9hic3 , aedae-q179r9 , aedae-u483 , aedae-j9hj23 , aedae-q17d68 , aedae-q177c7 , aedae-q0ifp1 , aedae-a0a1s4fx83 , aedae-a0a1s4g2m0 , aedae-q1hr49

Title : Functional annotation of a full-length mouse cDNA collection - Kawai_2001_Nature_409_685
Author(s) : Kawai J , Shinagawa A , Shibata K , Yoshino M , Itoh M , Ishii Y , Arakawa T , Hara A , Fukunishi Y , Konno H , Adachi J , Fukuda S , Aizawa K , Izawa M , Nishi K , Kiyosawa H , Kondo S , Yamanaka I , Saito T , Okazaki Y , Gojobori T , Bono H , Kasukawa T , Saito R , Kadota K , Matsuda H , Ashburner M , Batalov S , Casavant T , Fleischmann W , Gaasterland T , Gissi C , King B , Kochiwa H , Kuehl P , Lewis S , Matsuo Y , Nikaido I , Pesole G , Quackenbush J , Schriml LM , Staubli F , Suzuki R , Tomita M , Wagner L , Washio T , Sakai K , Okido T , Furuno M , Aono H , Baldarelli R , Barsh G , Blake J , Boffelli D , Bojunga N , Carninci P , de Bonaldo MF , Brownstein MJ , Bult C , Fletcher C , Fujita M , Gariboldi M , Gustincich S , Hill D , Hofmann M , Hume DA , Kamiya M , Lee NH , Lyons P , Marchionni L , Mashima J , Mazzarelli J , Mombaerts P , Nordone P , Ring B , Ringwald M , Rodriguez I , Sakamoto N , Sasaki H , Sato K , Schonbach C , Seya T , Shibata Y , Storch KF , Suzuki H , Toyo-oka K , Wang KH , Weitz C , Whittaker C , Wilming L , Wynshaw-Boris A , Yoshida K , Hasegawa Y , Kawaji H , Kohtsuki S , Hayashizaki Y
Ref : Nature , 409 :685 , 2001
Abstract : The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
ESTHER : Kawai_2001_Nature_409_685
PubMedSearch : Kawai_2001_Nature_409_685
PubMedID: 11217851
Gene_locus related to this paper: mouse-1lipg , mouse-1plip , mouse-1plrp , mouse-ABH15 , mouse-abhd5 , mouse-ABHD6 , mouse-Abhd8 , mouse-aryla , mouse-bphl , mouse-cauxin , mouse-Ces1g , mouse-CPMac , mouse-dpp8 , mouse-EPHX1 , mouse-ES10 , mouse-hslip , mouse-hyes , mouse-ABHD2 , mouse-lcat , mouse-lipli , mouse-LIPN , mouse-lypla1 , mouse-lypla2 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-Ppgb , mouse-PPME1 , mouse-ppt , mouse-q3uuq7 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-RISC , mouse-SERHL , mouse-SPG21 , mouse-Tex30

Title : Poster: Nerve growth factor utilizes common signaling pathways to differentially regulate M4 muscarinic and adenosine A2A receptor mRNA -
Author(s) : Malek RL , Lee NH
Ref : Life Sciences , 64 :567 , 1999
PubMedID:

Title : Nerve growth factor regulation of m4 muscarinic receptor mRNA stability but not gene transcription requires mitogen-activated protein kinase activity - Lee_1998_J.Biol.Chem_273_22317
Author(s) : Lee NH , Malek RL
Ref : Journal of Biological Chemistry , 273 :22317 , 1998
Abstract : Nerve growth factor (NGF) up-regulated steady-state levels of m4 muscarinic acetylcholine receptor (mAChR) mRNA in PC12 cells. Up-regulation of mRNA levels was associated with a corresponding increase in mAChR binding sites. Two other growth factors, basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF), up-regulated m4 mRNA and mAChR binding sites. Treatment of PC12 cells with NGF and bFGF, but not EGF, has previously been demonstrated to result in sustained activation of mitogen-activated protein kinase (MAPK). Analogously, NGF and bFGF, but not EGF, increased the stability of m4 mRNA in PC12 cells. In HER-PC12 cells, a clonal PC12 cell transfectant overexpressing EGF receptors and displaying sustained MAPK activation upon receptor stimulation, EGF treatment stabilized the m4 transcript. A synthetic inhibitor of MAPK kinase, PD98059, inhibited growth factor-induced stabilization of the m4 transcript in both PC12 and HER-PC12 cells. These findings demonstrate that the MAPK pathway is involved in transcript stabilization. Cycloheximide pretreatment abolished the post-transcriptional effect of NGF, indicating that de novo protein synthesis was required for the observed increase in m4 mRNA stability. By contrast, cycloheximide had no discernible post-transcriptional effect if added after NGF treatment, suggesting that an inducible yet stable protein factor was involved in m4 mRNA decay. An unusually well conserved 137 nucleotides of m4 3'-untranslated region has been identified by sequence comparison with other mRNAs that are post-transcriptionally regulated by NGF. In PC12 cells that heterologously overexpress this region, we demonstrate that NGF no longer stabilizes endogenous m4 mRNA. This conserved region probably represents an NGF-responsive element involved in mRNA stability regulation. Finally, transcription of the m4 gene can be induced by all three growth factors but is not dependent on MAPK activity, unlike growth factor-induced m4 mRNA stabilization.
ESTHER : Lee_1998_J.Biol.Chem_273_22317
PubMedSearch : Lee_1998_J.Biol.Chem_273_22317
PubMedID: 9712850

Title : Virus- and interferon-induced loss of inhibitory M2 muscarinic receptor function and gene expression in cultured airway parasympathetic neurons - Jacoby_1998_J.Clin.Invest_102_242
Author(s) : Jacoby DB , Xiao HQ , Lee NH , Chan-Li Y , Fryer AD
Ref : J Clinical Investigation , 102 :242 , 1998
Abstract : Viral infections increase vagally mediated reflex bronchoconstriction. Decreased function of inhibitory M2 muscarinic receptors on the parasympathetic nerve endings is likely to contribute to increased acetylcholine release. In this study, we used cultured airway parasympathetic neurons to determine the effects of parainfluenza virus and of interferon (IFN)-gamma on acetylcholine release, inhibitory M2 receptor function, and M2 receptor gene expression. In control cultures, electrically stimulated acetylcholine release increased when the inhibitory M2 receptors were blocked using atropine (10(-)5 M) and decreased when these receptors were stimulated using methacholine (10(-)5 M). Acetylcholine release was increased by viral infection and by treatment with IFN-gamma (300 U/ml). In these cells, atropine did not further potentiate, nor did methacholine inhibit, acetylcholine release, suggesting decreased inhibitory M2 receptor function and/or expression. Using a competitive reverse transcription-polymerase chain reaction method, we demonstrated that M2 receptor gene expression was decreased by more that an order of magnitude both by virus infection and by treatment with IFN. Thus, viral infections may increase vagally mediated bronchoconstriction both by directly inhibiting M2 receptor gene expression and by causing release of IFN-gamma which inhibits M2 receptor gene expression.
ESTHER : Jacoby_1998_J.Clin.Invest_102_242
PubMedSearch : Jacoby_1998_J.Clin.Invest_102_242
PubMedID: 9649578

Title : The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus - Klenk_1997_Nature_390_364
Author(s) : Klenk HP , Clayton RA , Tomb JF , White O , Nelson KE , Ketchum KA , Dodson RJ , Gwinn M , Hickey EK , Peterson JD , Richardson DL , Kerlavage AR , Graham DE , Kyrpides NC , Fleischmann RD , Quackenbush J , Lee NH , Sutton GG , Gill S , Kirkness EF , Dougherty BA , McKenney K , Adams MD , Loftus B , Peterson S , Reich CI , McNeil LK , Badger JH , Glodek A , Zhou L , Overbeek R , Gocayne JD , Weidman JF , McDonald L , Utterback T , Cotton MD , Spriggs T , Artiach P , Kaine BP , Sykes SM , Sadow PW , D'Andrea KP , Bowman C , Fujii C , Garland SA , Mason TM , Olsen GJ , Fraser CM , Smith HO , Woese CR , Venter JC
Ref : Nature , 390 :364 , 1997
Abstract : Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.
ESTHER : Klenk_1997_Nature_390_364
PubMedSearch : Klenk_1997_Nature_390_364
PubMedID: 9389475
Gene_locus related to this paper: arcfu-AF0514 , arcfu-AF0675 , arcfu-AF1134 , arcfu-AF1563 , arcfu-AF1753 , arcfu-AF1763 , arcfu-est1 , arcfu-est2 , arcfu-est3 , arcfu-estea , arcfu-o28594 , arcfu-o29442 , arcfu-pcbd

Title : Poster: Phenotypic interconversion of muscarinic receptor subtypes coupled to phospholipase C by exchanging two amino acids -
Author(s) : Geoghagen NS , Lee NH
Ref : Life Sciences , 60 :1177 , 1997
PubMedID:

Title : Poster: Loss of neuronal m2 muscarinic receptors with viral infection in cultured airway parasympathetic nerves -
Author(s) : Fryer AD , Lee NH , Jacoby DB
Ref : Life Sciences , 60 :1189 , 1997
PubMedID:

Title : Alanine scanning mutagenesis of conserved arginine\/lysine-arginine\/lysine-X-X-arginine\/lysine G protein-activating motifs on m1 muscarinic acetylcholine receptors - Lee_1996_Mol.Pharmacol_50_140
Author(s) : Lee NH , Geoghagen NS , Cheng E , Cline RT , Fraser CM
Ref : Molecular Pharmacology , 50 :140 , 1996
Abstract : Alanine scanning mutagenesis of B-B-X-X-B motifis (where B is a basic residue and X is any nonbasic residue) in m1 muscarinic acetylcholine receptors was performed to determine the relative roles of basic amino acids in receptor coupling. This conserved motif is found in many G protein-coupled receptors and has been implicated in G protein activation. The KKAAR365 motif, located at the carboxyl-terminal third intracellular loop of m1 receptors, was mutated to AAAAA365, thereby generating a triple-substitution mutant devoid of ability to stimulate either phosphoinositide (PI) hydrolysis or cAMP accumulation. In contrast, a triple-alanine substitution of the KRTPR140 motif in the carboxyl-terminal second intracellular loop, yielding mutant AATPA140, had no effect on receptor coupling to the two independent second messenger pathways. Analysis of a series of single- and double-substitution mutants demonstrate that all three basic residues of the KKAAR365 motif participate in efficient m1 receptor coupling. The presence of second and third basic residues in this motif was absolutely critical for full agonist recognition of a high and low affinity state of the receptor. Mutation of either Lys362 or Lys365, but not-Lys361, abolished guanine nucleotide-dependent conversion of agonist affinity states and correlated with an inability of full agonists to fully activate PI hydrolysis. The different combinatorial double-substitution mutants also revealed that Lys365 was necessary but not sufficient, in the context of the KKAAR365 motif, for efficient receptor coupling. This residue cannot facilitate full agonist-stimulated Pl hydrolysis in the absence of both Lys361 and Lys362. In comparison, the critical residue Lys362 was both necessary and sufficient. Substitution of nearby basic residues Lys361 and Lys365 with alanine yielded mutant AKAAA365, which exhibited partial ability to couple PI hydrolysis after full agonist stimulation. Therefore, Lys365 seems to function in a hierarchal (interdependent) manner with nearby basic residues, whereas Lys361 and Lys362 can act independent of surrounding basic residues to facilitate partial m1 receptor coupling after full agonist stimulation. In contrast, all three residues must be present for stimulation of PI hydrolysis by a partial agonist.
ESTHER : Lee_1996_Mol.Pharmacol_50_140
PubMedSearch : Lee_1996_Mol.Pharmacol_50_140
PubMedID: 8700106

Title : Poster: Regulation of muscarinic acetylcholine receptor subtype expression by post-transcriptional and post-translational mechanisms -
Author(s) : Lee NH
Ref : Life Sciences , 56(11-12) :1027 , 1995
PubMedID:

Title : Regulation of muscarinic receptor expression by changes in mRNA stability - Fraser_1995_Life.Sci_56(11-12)_899
Author(s) : Fraser CM , Lee NH
Ref : Life Sciences , 56(11-12) :899 , 1995
Abstract : Regulation of muscarinic acetylcholine receptor (mAChR) subtype mRNAs was investigated in the human neuroblastoma cell line IMR-32 and in transfected CHO cells. IMR-32 cells express both m1 and m3 subtypes of mAChR. Exposure of IMR-32 cells to the muscarinic agonist, carbamylcholine (CBC) leads to a time dependent down-regulation of mAChRs which was maximal by 9 hours. mAChR activation resulted in a differential regulation of mAChR subtype mRNAs. m1 mAChR mRNA was down-regulated following 12 hours of agonist treatment and was associated with a decreased stability of the receptor transcript. In contrast, the m3 mAChR mRNA was resistant to agonist treatment for up to 24 hours. Using transfected CHO cells, we identified sequence elements within the 3'-untranslated region (3'-UTR) of the m1 mAChR gene which dictate agonist-induced destabilization of the m1 mAChR mRNA. Removal of these sequences abolished the ability of chronic agonist exposure to destabilize m1 mAChR mRNA. These findings suggest that sequence specific differences between m1 and m3 mAChR subtypes, which both preferentially couple to hydrolysis of phosphoinositides, may be responsible for differences in the regulation of mAChR gene expression.
ESTHER : Fraser_1995_Life.Sci_56(11-12)_899
PubMedSearch : Fraser_1995_Life.Sci_56(11-12)_899
PubMedID: 10188791

Title : Agonist-mediated destabilization of m1 muscarinic acetylcholine receptor mRNA. Elements involved in mRNA stability are localized in the 3'-untranslated region - Lee_1994_J.Biol.Chem_269_4291
Author(s) : Lee NH , Earle-Hughes J , Fraser CM
Ref : Journal of Biological Chemistry , 269 :4291 , 1994
Abstract : The effects of chronic agonist exposure on receptor number (down-regulation) have been shown, in part, to be due to effects on mRNA levels. Agonist-mediated effects on muscarinic acetylcholine receptor (mAChR) mRNA were investigated in Chinese hamster ovary (CHO) cells stably transfected with m1 mAChR gene constructs containing the open reading frame and a series of deletions of the flanking 3'-untranslated region (3'-UTR). Carbachol (CBC) down-regulated m1 mAChRs encoded by the construct m1C1, an m1 mAChR transcript containing the entire flanking 3'UTR (nucleotides 1526-2622), in a time-dependent fashion with maximal decreases occurring by 12 h. Steady-state levels of m1C1 mRNA declined in a parallel fashion beginning 6 h after CBC pretreatment. Similar findings were obtained with m1C2, a construct which is missing all but 261 bases of flanking 3'-UTR (nucleotides (nt) 1526-1786). Since the rate of mRNA degradation represents an important potential regulatory mechanism to control the level of gene expression, we investigated the effects of CBC treatment on m1C1 and m1C2 mRNA stability. The half-life of either transcript in untreated cells was approximately 14 h, whereas m1C1 and m1C2 transcript half-lives decreased to approximately 3 h in cells treated with CBC. Agonist-induced destabilization of m1C2 mRNA could be mimicked by phorbol esters in a concentration-dependent manner and blocked by the protein kinase inhibitor, H-7. In contrast, m1 mAChR mRNA constructs missing nt 1526-1786 of the 3'-UTR (m1C3 and m1C4) did not undergo agonist- or phorbol ester-induced destabilization. In the neuroblastoma cell line IMR-32, endogenous m1 mAChR mRNA was down-regulated and destabilized following CBC treatment. These results demonstrate that agonist-induced mRNA destabilization is a potential mechanism for regulating m1 mAChR levels. Furthermore, deletion studies identify a 261 base region of the 3'-UTR having the potential to form stable stem-loop structures which likely harbors element(s) responsible for message destabilization.
ESTHER : Lee_1994_J.Biol.Chem_269_4291
PubMedSearch : Lee_1994_J.Biol.Chem_269_4291
PubMedID: 8307995

Title : Cross-talk between m1 muscarinic acetylcholine and beta 2-adrenergic receptors. cAMP and the third intracellular loop of m1 muscarinic receptors confer heterologous regulation - Lee_1993_J.Biol.Chem_268_7949
Author(s) : Lee NH , Fraser CM
Ref : Journal of Biological Chemistry , 268 :7949 , 1993
Abstract : Genes encoding the m1 muscarinic (m1 mAChR) and beta 2-adrenergic receptors (beta 2AR) were stably co-expressed into Chinese hamster ovary (CHO) cells to study receptor regulation and cross-talk. Persistent activation of the beta 2AR/adenylate cyclase pathway by isoproterenol leads to heterologous desensitization, internalization, and down-regulation of the m1 mAChR which is comparable, but smaller in magnitude, with that seen with persistent activation of the m1 mAChR by carbachol. This heterologous effect was mimicked by dibutyryl cAMP and forskolin and antagonized by the protein kinase A (PKA) inhibitor H-8. A potential consensus sequence for phosphorylation by PKA (Lys351-Arg-Lys-Thr354) exists on the third intracellular loop of the m1 mAChR, suggesting that receptor phosphorylation by PKA may be involved in heterologous regulation. The loss of m1 mAChRs induced by carbachol was not reversed by H-8, indicating that homologous regulation is not dependent on PKA. Recent evidence suggests that muscarinic agonist-mediated internalization of the m1 mAChR involves the third intracellular loop (i3) (Maeda, S., Lameh, J., Mallet, W. G., Philip, M., Ramachandran, J., and Sadee, W. (1990) FEBS Lett. 269, 386-388). Three deletion mutant receptors were constructed in which the majority, or small regions, of i3 were eliminated but the membrane proximal portions of the loop were left intact. Each of the mutants was co-expressed with the beta 2AR in CHO cells. A small region in i3 was identified which is crucial for carbachol- and isoproterenol-promoted internalization and down-regulation. This region contains a series of 6 serine residues within an 8-amino acid stretch. A similar domain has been identified in the carboxyl tail of the beta 2AR and has been proposed to participate in receptor internalization (Hausdorff, W. P., Campbell, P. T., Ostrowski, J., Yu, S. S., Caron, M. G., and Lefkowitz, R. J. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 2979-2983).
ESTHER : Lee_1993_J.Biol.Chem_268_7949
PubMedSearch : Lee_1993_J.Biol.Chem_268_7949
PubMedID: 8385129

Title : Effects of tacrine on brain muscarinic-receptor-mediated second-messenger signals - Kiefer-Day_1993_Pharmacology_47_98
Author(s) : Kiefer-Day JS , Abdallah ES , Forray C , Lee NH , Kim ON , El-Fakahany EE
Ref : Pharmacology , 47 :98 , 1993
Abstract : The purpose of this study was to investigate the effects of 9-amino-1,2,3,4-tetrahydroacridine (THA; Tacrine) on muscarinic-receptor-linked second-messenger systems in rat brain and to determine the selectivity and mechanisms of these effects. Both competitive and noncompetitive antagonism was revealed in saturation radioligand binding studies performed in cortical and striatal tissue, depending on THA concentration. Micromolar THA concentrations blocked muscarinic-receptor-mediated inhibition of cAMP formation and stimulation of phosphoinositide (PI) hydrolysis with poor selectivity between the two responses. While both responses were blocked in the same concentration range (4-60 mumol/l), non-competitive antagonism of PI hydrolysis occurred at THA concentrations greater than 10 mumol/l while competitive antagonism was displayed for the cAMP response at concentrations of THA up to 40 mumol/l. THA was equally effective at inhibiting PI hydrolysis stimulated by histamine, phenylephrine or oxotremorine-M, when these agonists were employed in concentrations equal to their EC50s for the response. THA did not antagonize PI hydrolysis mediated by the quisqualate receptor at any agonist concentration used. Furthermore, THA blocked carbachol- but not morphine-induced inhibition of forskolin-stimulated cAMP formation in the striatum.
ESTHER : Kiefer-Day_1993_Pharmacology_47_98
PubMedSearch : Kiefer-Day_1993_Pharmacology_47_98
PubMedID: 8395061

Title : Poster: Post-transcriptional regulation of the m1 muscarinic acetylcholine receptor -
Author(s) : Lee NH , Fraser CM
Ref : Life Sciences , 52(5-6) :562 , 1993
PubMedID:

Title : Modulation by certain conserved aspartate residues of the allosteric interaction of gallamine at the m1 muscarinic receptor - Lee_1992_J.Pharmacol.Exp.Ther_262_312
Author(s) : Lee NH , Hu J , El-Fakahany EE
Ref : Journal of Pharmacology & Experimental Therapeutics , 262 :312 , 1992
Abstract : Muscarinic acetylcholine receptors belong to a superfamily of G-protein coupled receptors and contain within their structure several conserved aspartate residues. These residues have been implicated to play important roles in the interaction of agonists and their competitive antagonists with the receptor. In the present work, we investigated whether the same residues might also serve as important contact points for allosteric antagonists of muscarinic receptors, because the majority of these compounds are cationic in nature, or if such residues are involved in modification of receptor conformation by these antagonists. Gallamine was used as a prototype for these antagonists. Site-directed mutagenesis of the m1 muscarinic receptor subtype was utilized to define some of the molecular determinants involved in cooperative allosteric interactions. We report that substitution of the aspartate residue at position 71, but not at positions 99 and 122 with asparagine, affected the affinity of gallamine for the unliganded m1 receptor. A similar substitution at positions 71 and 99 decreased the magnitude of its cooperative effects on the binding of [3H]N-methylscopolamine. Our data suggest that these residues are implicated in cooperative interactions. At present, however, we cannot discount a more pivotal role of other residues on the receptor sequence in allosteric interactions. The data also support the notion that different molecular entities are required for the binding of allosteric antagonists as compared to the interaction of agonists and competitive antagonists at the receptor.
ESTHER : Lee_1992_J.Pharmacol.Exp.Ther_262_312
PubMedSearch : Lee_1992_J.Pharmacol.Exp.Ther_262_312
PubMedID: 1625205

Title : Allosteric interactions at the m1, m2 and m3 muscarinic receptor subtypes - Lee_1991_J.Pharmacol.Exp.Ther_256_468
Author(s) : Lee NH , El-Fakahany EE
Ref : Journal of Pharmacology & Experimental Therapeutics , 256 :468 , 1991
Abstract : The purpose of our study was to investigate the interactions of allosteric antagonists at the individual m1, m2 and m3 muscarinic receptor subtypes. This was achieved through the use of transformed Chinese hamster ovary cells stably expressing the rat m1 or m3 receptor genes. A homogeneous population of the m2 subtype was obtained from rat heart tissue. Our data indicate that the cardioselective antagonists (gallamine, methoctramine, AF-DX 116 and himbacine) display the following rank order of potency for both displacing ligand binding to the primary site on the receptor and allosterically decelerating ligand dissociation: m2 greater than m1 greater than m3. Schild analysis showed the following rank order of the magnitude of gallamine's cooperative interactions with the three receptor subtypes: m3 greater than m1 greater than m2. By comparison, the ion-channel blockers (verapamil, phencyclidine and quinidine) exhibited a rank order of potency for cooperative effects similar to that of cardioselective antagonists; however, these blockers did not show appreciable specificity in their interaction with the receptor primary binding site. There was a lack of correlation between the displacement of ligand binding and the allosteric potencies of the allosteric antagonists at each of the three muscarinic receptor subtypes, thus revealing the complex nature of interaction (both competitive and allosteric) between many of these compounds with the muscarinic receptor. Despite the fact that the majority of allosteric muscarinic antagonists are also K+ channel blockers, the use of pertussis toxin did not support the notion that this channel represents the allosteric site coupled to the receptor.
ESTHER : Lee_1991_J.Pharmacol.Exp.Ther_256_468
PubMedSearch : Lee_1991_J.Pharmacol.Exp.Ther_256_468
PubMedID: 1993991

Title : Allosteric antagonists of the muscarinic acetylcholine receptor -
Author(s) : Lee NH , El-Fakahany EE
Ref : Biochemical Pharmacology , 42 :199 , 1991
PubMedID: 1859442

Title : The allosteric binding profile of himbacine: a comparison with other cardioselective muscarinic antagonists - Lee_1990_Eur.J.Pharmacol_179_225
Author(s) : Lee NH , El-Fakahany EE
Ref : European Journal of Pharmacology , 179 :225 , 1990
Abstract : The possibility of an allosteric interaction by himbacine, a cardioselective antagonist, with rat cardiac muscarinic receptors was studied. Himbacine allosterically decelerated the dissociation of bound [3H]N-methylscopolamine [( 3H]NMS) in a concentration-dependent manner with an IC50 value of 103.7 microM. When compared to the IC50 values of other cardioselective antagonists, the rank order of potencies was: methoctramine greater than gallamine greater than himbacine greater than AF-DX 116. In contrast, the potencies of these compounds to displace [3H]NMS binding were: himbacine greater than methoctramine greater than AF-DX 116 greater than gallamine. The allosteric potencies were found not to be correlated with binding potencies (correlation coefficient = -0.15). A striking common feature of the cardioselective antagonists is their ability to bind to an allosteric site on cardiac muscarinic receptors.
ESTHER : Lee_1990_Eur.J.Pharmacol_179_225
PubMedSearch : Lee_1990_Eur.J.Pharmacol_179_225
PubMedID: 2364985

Title : Methoctramine, a cardioselective muscarinic antagonist, stimulates phosphoinositide hydrolysis in rat cerebral cortex - Lee_1989_Eur.J.Pharmacol_167_295
Author(s) : Lee NH , Forray C , El-Fakahany EE
Ref : European Journal of Pharmacology , 167 :295 , 1989
Abstract : The cardioselective muscarinic antagonist methoctramine antagonized carbamylcholine-mediated phosphoinositide (PI) hydrolysis in a concentration-dependent fashion in dissociated rat cerebrocortical cells. However, as the concentration of methoctramine was increased above 5 microM, there was a reversal of the antagonism of the PI response. In the absence of carbamylcholine, methoctramine by itself significantly increased PI hydrolysis with a maximal effect at 30 microM. Various classes of receptor antagonists, including atropine, and ion-channel blockers were unable to block methoctramine-stimulated PI hydrolysis.
ESTHER : Lee_1989_Eur.J.Pharmacol_167_295
PubMedSearch : Lee_1989_Eur.J.Pharmacol_167_295
PubMedID: 2556288

Title : Different mechanisms of antagonism by methoctramine of two neuronal muscarinic receptor-mediated second messenger responses - Lee_1989_J.Pharmacol.Exp.Ther_251_992
Author(s) : Lee NH , Fryer AD , Forray C , El-Fakahany EE
Ref : Journal of Pharmacology & Experimental Therapeutics , 251 :992 , 1989
Abstract : The allosteric effects and subtype selectivity of methoctramine on neuronal muscarinic receptors in N1E-115 cells and two different rat brain regions (cerebral cortex and striatum) were assessed. Saturation isotherms of [3H]N-methylscopolamine binding, performed in N1E-115 cells and dissociated cerebral cortex, showed that methoctramine reduced the Bmax in a concentration-dependent manner. Furthermore, this compound slowed the rate of dissociation of bound [3H]N-methylscopolamine in the same tissue preparations. Low concentrations of methoctramine (less than or equal to 1 microM) antagonized the M1-linked phosphoinositide response in N1E-115 cells and dissociated cerebral cortex in an apparent competitive mechanism. However, methoctramine exhibited noncompetitive effects at higher concentrations in N1E-115 cells. Observation of a similar effect in cerebrocortical cells was precluded since methoctramine by itself, at concentrations higher than 1 microM, stimulated inositol phosphate formation. The stimulatory effect of methoctramine on phosphoinositide hydrolysis was not blocked by atropine. A solely competitive mode of antagonism by methoctramine was observed for the inhibition of cAMP formation (a noncardiac-M2 coupled response) in N1E-115 cells and dissociated striatum. This antagonism was evident even at concentrations of methoctramine that noncompetitively antagonized the M1 response. Anomalously, methoctramine alone inhibited cAMP formation in dissociated striatum at concentrations of greater than or equal to 30 microM. Atropine was ineffective at blocking this effect. Methoctramine failed to demonstrate muscarinic receptor subtype selectively in blocking these two second messenger responses. This nonselectivity was supported by indirect binding experiments involving methoctramine and [3H]N-methylscopolamine. The data presented here demonstrate that methoctramine binds to a secondary site(s) associated with neuronal muscarinic receptors. Furthermore, methoctramine exhibits different mechanisms of antagonism and displays poor selectivity for the M1-linked phosphoinositide and noncardiac-M2 linked cAMP responses.
ESTHER : Lee_1989_J.Pharmacol.Exp.Ther_251_992
PubMedSearch : Lee_1989_J.Pharmacol.Exp.Ther_251_992
PubMedID: 2557423

Title : Mixed competitive and allosteric antagonism by gallamine of muscarinic receptor-mediated second messenger responses in N1E-115 neuroblastoma cells - Lee_1989_J.Neurochem_53_1300
Author(s) : Lee NH , El-Fakahany EE
Ref : Journal of Neurochemistry , 53 :1300 , 1989
Abstract : The antagonistic effects of gallamine on muscarinic receptor-linked responses were investigated in N1E-115 neuroblastoma cells. M1 muscarinic receptor-mediated phosphoinositide hydrolysis induced by carbamylcholine was antagonized by gallamine, with a Ki value of 33 microM. By comparison, gallamine was four- to fivefold less potent in blocking noncardiac M2 muscarinic receptor-mediated inhibition of cyclic AMP formation, with a Ki value of 144 microM. The resulting Arunlakshana-Schild plots of the antagonism of both responses by gallamine were linear and exhibited slopes not differing from 1, a result indicative of a competitive mechanism. To elucidate further the nature of gallamine's inhibitory actions, experiments were performed where the effects of gallamine in combination with the known competitive muscarinic antagonist, N-methylscopolamine (NMS), were studied. In the presence of both antagonists, a supraadditive shift in the carbamylcholine dose-response curve was demonstrated for the two responses, a result suggestive of an allosteric mode of interaction between gallamine and NMS binding sites. Confirmation that gallamine allosterically modifies the muscarinic receptor was provided by radioligand binding studies. Gallamine competition curves with either [N-methyl-3H]scopolamine methyl chloride ([3H]NMS) or [N-methyl-3H]quinuclidinyl benzilate methyl chloride ([3H]NMeQNB) were unusually shallow. Furthermore, gallamine decelerated the rate of dissociation of receptor-bound [3H]NMS greater than [3H]NMeQNB in a dose-dependent manner. The present study demonstrates that whereas gallamine antagonizes carbamylcholine-mediated responses in N1E-115 cells in a competitive manner, an allosteric component of its action is revealed in the presence of muscarinic antagonists such as NMS.
ESTHER : Lee_1989_J.Neurochem_53_1300
PubMedSearch : Lee_1989_J.Neurochem_53_1300
PubMedID: 2549200

Title : Effects of aging on the interaction of quinuclidinyl benzilate, N-methylscopolamine, pirenzepine, and gallamine with brain muscarinic receptors - Surichamorn_1988_Neurochem.Res_13_1183
Author(s) : Surichamorn W , Kim ON , Lee NH , Lai WS , El-Fakahany EE
Ref : Neurochem Res , 13 :1183 , 1988
Abstract : The objective of the present study was to investigate the effects of senescence on the binding characteristics of muscarinic receptors by using [3H]quinuclidinyl benzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]NMS) as ligands in young (3 months), middle-age (10 months) and old (24 months) male Fischer 344 rats. Muscarinic receptor density was found to decrease significantly with aging in certain brain regions, depending on the ligand employed. Moreover, the relative proportions of M1 and M2 muscarinic receptor subtypes was not significantly altered by aging, except in the aged striatum. Furthermore, the dissociation kinetics of [3H]NMS in the cerebral cortex and their allosteric modulation by gallamine were only slightly influenced by age.
ESTHER : Surichamorn_1988_Neurochem.Res_13_1183
PubMedSearch : Surichamorn_1988_Neurochem.Res_13_1183
PubMedID: 3237310

Title : Non-selectivity of amitriptyline for subtypes of brain muscarinic receptors demonstrated in binding and functional assays - McKinney_1988_Eur.J.Pharmacol_157_51
Author(s) : McKinney M , Lee NH , Anderson DJ , Vella-Rountree L , El-Fakahany EE
Ref : European Journal of Pharmacology , 157 :51 , 1988
Abstract : The characteristics of interaction of amitriptyline, a tricyclic antidepressant, with rat brain muscarinic receptors were assessed using both radioligand binding and functional assays. In competition studies, amitriptyline displaced muscarinic ligand binding from a single high-affinity site in homogenates of various brain regions which have a different distribution of M1 and M2 receptor subtypes. The affinity of amitriptyline for muscarinic receptors was also comparable in all brain regions. Furthermore, amitriptyline identified a single species of muscarinic receptors in intact cells dissociated from the cerebral cortex and in cerebrocortical slices. The non-selectivity of amitriptyline for muscarinic receptor subtypes in these preparations was in contrast to the selectivity exhibited by pirenzepine. This non-selective nature of amitriptyline was also evident in functional assays, since this antidepressant was equipotent at antagonizing M1-mediated increase in phosphoinositide hydrolysis and M2-mediated inhibition of cyclic AMP formation in dissociated cortical cells. Atropine was also equipotent at blocking both responses but was 20- to 30-fold more potent than amitriptyline. These results demonstrate that amitriptyline behaves as a non-selective muscarinic antagonist using both radioligand binding and functional measurements.
ESTHER : McKinney_1988_Eur.J.Pharmacol_157_51
PubMedSearch : McKinney_1988_Eur.J.Pharmacol_157_51
PubMedID: 2853074

Title : Influence of ligand choice on the apparent binding profile of gallamine to cardiac muscarinic receptors. Identification of three main types of gallamine-muscarinic receptor interactions - Lee_1988_J.Pharmacol.Exp.Ther_246_829
Author(s) : Lee NH , El-Fakahany EE
Ref : Journal of Pharmacology & Experimental Therapeutics , 246 :829 , 1988
Abstract : The binding profile of the positively charged muscarinic antagonist, gallamine, was studied in rat heart homogenates. A proportion of the binding sites labeled by the tertiary muscarinic ligands [( 3H]quinuclidinyl benzilate (QNB) and [3H]atropine) were inaccessible to their quaternary analogs [( 3H]N-methyl-QNB (NMeQNB) and [3H]-N-methylscopolamine (NMS)] or gallamine. Whereas gallamine displaced the binding of [3H]NMeQNB with high affinity, biphasic competition curves were observed using [3H]NMS only at higher ligand concentrations. The rank order of potency of gallamine in allosterically decelerating ligand dissociation kinetics was: [3H]NMS greater than [3H]atropine greater than [3H]NMeQNB greater than [3H]QNB. Our calculations demonstrate that the displayed heterogeneity of gallamine binding sites detected using [3H]NMS, but not the tertiary ligands, might be accounted for by the allosteric modification of the binding of this ligand by gallamine. Based on these findings, the exhibited binding profile of gallamine to muscarinic receptors is influenced strongly by ligand choice, and also by the ligand concentration used in the binding experiment. Furthermore, it is concluded that gallamine binds to three major sites on the muscarinic receptor, thereby revealing an apparent heterogeneity of its binding sites, even in a tissue which presumably possesses one major muscarinic receptor subtype such as the heart. According to several lines of evidence, gallamine binds competitively and with high affinity to NMS-accessible sites on the receptor. Under certain experimental conditions, it also appears to identify another low-affinity site, either due to its binding to NMS-inaccessible sites or through its differential ability to alter the binding of ligands to the main binding domain on the receptor in an allosteric fashion.
ESTHER : Lee_1988_J.Pharmacol.Exp.Ther_246_829
PubMedSearch : Lee_1988_J.Pharmacol.Exp.Ther_246_829
PubMedID: 3418516

Title : Charge but not chemical class explains the selective binding of [3H]N-methylscopolamine to a subpopulation of [3H]quinuclidinyl benzilate binding sites in rat cerebral cortex homogenates -
Author(s) : Lee NH , Ramkumar V , El-Fakahany EE
Ref : European Journal of Pharmacology , 130 :153 , 1986
PubMedID: 3780857