Graham D

References (5)

Title : Determination of Intracellular Esterase Activity Using Ratiometric Raman Sensing and Spectral Phasor Analysis - Braddick_2023_Anal.Chem__
Author(s) : Braddick HJ , Tipping WJ , Wilson LT , Jaconelli HS , Grant EK , Faulds K , Graham D , Tomkinson NCO
Ref : Analytical Chemistry , : , 2023
Abstract : Carboxylesterases (CEs) are a class of enzymes that catalyze the hydrolysis of esters in a variety of endogenous and exogenous molecules. CEs play an important role in drug metabolism, in the onset and progression of disease, and can be harnessed for prodrug activation strategies. As such, the regulation of CEs is an important clinical and pharmaceutical consideration. Here, we report the first ratiometric sensor for CE activity using Raman spectroscopy based on a bisarylbutadiyne scaffold. The sensor was shown to be highly sensitive and specific for CE detection and had low cellular cytotoxicity. In hepatocyte cells, the ratiometric detection of esterase activity was possible, and the result was validated by multimodal imaging with standard viability stains used for fluorescence microscopy within the same cell population. In addition, we show that the detection of localized ultraviolet damage in a mixed cell population was possible using stimulated Raman scattering microscopy coupled with spectral phasor analysis. This sensor demonstrates the practical advantages of low molecular weight sensors that are detected using ratiometric Raman imaging and will have applications in drug discovery and biomedical research.
ESTHER : Braddick_2023_Anal.Chem__
PubMedSearch : Braddick_2023_Anal.Chem__
PubMedID: 36926851

Title : SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile - Biton_2007_Neuropsychopharmacology_32_1
Author(s) : Biton B , Bergis OE , Galli F , Nedelec A , Lochead AW , Jegham S , Godet D , Lanneau C , Santamaria R , Chesney F , Leonardon J , Granger P , Debono MW , Bohme GA , Sgard F , Besnard F , Graham D , Coste A , Oblin A , Curet O , Vige X , Voltz C , Rouquier L , Souilhac J , Santucci V , Gueudet C , Francon D , Steinberg R , Griebel G , Oury-Donat F , George P , Avenet P , Scatton B
Ref : Neuropsychopharmacology , 32 :1 , 2007
Abstract : In this paper, we report on the pharmacological and functional profile of SSR180711 (1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester), a new selective alpha7 acetylcholine nicotinic receptor (n-AChRs) partial agonist. SSR180711 displays high affinity for rat and human alpha7 n-AChRs (K(i) of 22+/-4 and 14+/-1 nM, respectively). Ex vivo (3)[H]alpha-bungarotoxin binding experiments demonstrate that SSR180711 rapidly penetrates into the brain (ID(50)=8 mg/kg p.o.). In functional studies performed with human alpha7 n-AChRs expressed in Xenopus oocytes or GH4C1 cells, the compound shows partial agonist effects (intrinsic activity=51 and 36%, EC(50)=4.4 and 0.9 microM, respectively). In rat cultured hippocampal neurons, SSR180711 induced large GABA-mediated inhibitory postsynaptic currents and small alpha-bungarotoxin sensitive currents through the activation of presynaptic and somato-dendritic alpha7 n-AChRs, respectively. In mouse hippocampal slices, the compound increased the amplitude of both glutamatergic (EPSCs) and GABAergic (IPSCs) postsynaptic currents evoked in CA1 pyramidal cells. In rat and mouse hippocampal slices, a concentration of 0.3 muM of SSR180711 increased long-term potentiation (LTP) in the CA1 field. Null mutation of the alpha7 n-AChR gene totally abolished SSR180711-induced modulation of EPSCs, IPSCs and LTP in mice. Intravenous administration of SSR180711 strongly increased the firing rate of single ventral pallidum neurons, extracellularly recorded in anesthetized rats. In microdialysis experiments, administration of the compound (3-10 mg/kg i.p.) dose-dependently increased extracellular acetylcholine (ACh) levels in the hippocampus and prefrontal cortex of freely moving rats. Together, these results demonstrate that SSR180711 is a selective and partial agonist at human, rat and mouse alpha7 n-AChRs, increasing glutamatergic neurotransmission, ACh release and LTP in the hippocampus.
ESTHER : Biton_2007_Neuropsychopharmacology_32_1
PubMedSearch : Biton_2007_Neuropsychopharmacology_32_1
PubMedID: 17019409

Title : SSR591813, a novel selective and partial alpha4beta2 nicotinic receptor agonist with potential as an aid to smoking cessation - Cohen_2003_J.Pharmacol.Exp.Ther_306_407
Author(s) : Cohen C , Bergis OE , Galli F , Lochead AW , Jegham S , Biton B , Leonardon J , Avenet P , Sgard F , Besnard F , Graham D , Coste A , Oblin A , Curet O , Voltz C , Gardes A , Caille D , Perrault G , George P , Soubrie P , Scatton B
Ref : Journal of Pharmacology & Experimental Therapeutics , 306 :407 , 2003
Abstract : (5aS,8S,10aR)-5a,6,9,10-Tetrahydro,7H,11H-8,10a-methanopyrido[2',3':5,6]pyrano[2, 3-d]azepine (SSR591813) is a novel compound that binds with high affinity to the rat and human alpha4beta2 nicotinic acetylcholine receptor (nAChR) subtypes (Ki = 107 and 36 nM, respectively) and displays selectivity for the alpha4beta2 nAChR (Ki, human alpha3beta4 > 1000, alpha3beta2 = 116; alpha1beta1deltagamma > 6000 nM and rat alpha7 > 6000 nM). Electrophysiological experiments indicate that SSR591813 is a partial agonist at the human alpha4beta2 nAChR subtype (EC50 = 1.3 micro M, IA =19% compared with the full agonist 1,1-dimethyl-4-phenyl-piperazinium). In vivo findings from microdialysis and drug discrimination studies confirm the partial intrinsic activity of SSR591813. The drug increases dopamine release in the nucleus accumbens shell (30 mg/kg i.p.) and generalizes to nicotine or amphetamine (10-20 mg/kg i.p.) in rats, with an efficacy approximately 2-fold lower than that of nicotine. Pretreatment with SSR591813 (10 mg/kg i.p.) reduces the dopamine-releasing and discriminative effects of nicotine. SSR591813 shows activity in animal models of nicotine dependence at doses devoid of unwanted side effects typically observed with nicotine (hypothermia and cardiovascular effects). The compound (10 mg/kg i.p.) also prevents withdrawal signs precipitated by mecamylamine in nicotine-dependent rats and partially blocks the discriminative cue of an acute precipitated withdrawal. SSR591813 (20 mg/kg i.p.) reduces i.v. nicotine self-administration and antagonizes nicotine-induced behavioral sensitization in rats. The present results confirm important role for alpha4beta2 nAChRs in mediating nicotine dependence and suggest that SSR591813, a partial agonist at this particular nAChR subtype, may have therapeutic potential in the clinical management of smoking cessation.
ESTHER : Cohen_2003_J.Pharmacol.Exp.Ther_306_407
PubMedSearch : Cohen_2003_J.Pharmacol.Exp.Ther_306_407
PubMedID: 12682217

Title : Identification of polypeptides associated with a putative neuronal nicotinic acetylcholine receptor - Betz_1982_J.Biol.Chem_257_11390
Author(s) : Betz H , Graham D , Rehm H
Ref : Journal of Biological Chemistry , 257 :11390 , 1982
Abstract : Polypeptides involved in the binding of the nicotinic acetylcholine receptor ligand alpha-bungarotoxin (Mr = 8,000) to neuronal membranes were identified by three independent methods: (i) 125I-alpha-bungarotoxin bound to membrane fractions or to monolayer cultures of chick retina was cross-linked to its binding site by using glutaraldehyde, or the photoactivatable bifunctional reagent N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate. Electrophoretic analysis of the cross-linked membrane proteins revealed 125I-alpha-bungarotoxin-polypeptide adducts of apparent Mr = 63,000, 43,000, and 33,000. (ii) Affinity purification of the alpha-bungarotoxin binding protein from detergent extracts of [35S]methionine-labeled retina cultures identified one major polypeptide with an Mr = 57,000. (iii) Indirect immunoprecipitation from detergent extracts of [35S]methionine-labeled rat pheochromocytoma cells (PC 12) gave evidence for a specific co-precipitation of alpha-bungarotoxin with three polypeptides (Mr = 57,000, 34,000, and 25,000). The data suggest that polypeptides of Mr - 57,000, 35,000, and 25,000 (+/- 3,000) are located at or close to the alpha-bungarotoxin binding domain of the putative neuronal nicotinic acetylcholine receptor.
ESTHER : Betz_1982_J.Biol.Chem_257_11390
PubMedSearch : Betz_1982_J.Biol.Chem_257_11390
PubMedID: 7118888

Title : Changes in the sensitivity to cholinomimetic drugs of smooth and cardiac muscle in the rat induced by subacute administration of di-isopropyl phosphorofluoridate -
Author(s) : Graham D , Madden J , Mitchelson F
Ref : European Journal of Pharmacology , 23 :27 , 1973
PubMedID: 4733770