Wang DX

References (6)

Title : [Effect of lidocaine on the impairment of learning and memory function and central cholinergic system after transient global cerebral ischemia in mice] - Song_2006_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_38_164
Author(s) : Song PP , Wang DX , Wang PY , Zuo PP
Ref : Beijing Da Xue Xue Bao Yi Xue Ban , 38 :164 , 2006
Abstract : OBJECTIVE: To evaluate the effects of lidocaine on the impairments of learning and memorial function and central cholinergic system after transient global cerebral ischemia in mice of different apolipoprotein E genotypes.
METHODS: Transient global ischemia was induced by bilateral common carotid arteries occlusion (BCCAO) for 17 minutes. Healthy male C57BL/6J wild-type mice (C57 mice) and apolipoprotein E knockout mice (ApoE mice) were randomly divided into six groups: C57 control group (sham operation, neither BCCAO was performed nor pharmacologic intervention was given), C57 ischemia group (BCCAO for 17 minutes was performed and normal saline was given intraperitoneally), C57 lidocaine group (BCCAO for 17 minutes was performed and lidocaine was given intraperitoneally), ApoE control group (the same procedure as that of C57 control group), ApoE ischemia group (the same procedure as that of C57 ischemia group), ApoE lidocaine group (the same procedure as that of C57 lidocaine group). The mice were allowed to recover for 7 days. Morris water maze test were performed from the 8th postoperative day. Mice were tested four times daily for 5 consecutive days. The latency periods were recorded and the percentages of effective search strategies were calculated. On the 12th postoperative day after Morris water maze test, mice were decapitated under anesthesia. The cerebral cortex and hippocampus were removed quickly. The activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) as well as the binding activity of muscarinic receptor (M receptor) were assayed.
RESULTS: (1) The latency periods were significantly longer in the ischemia groups than in the corresponding control groups (P<0.05 or 0.01). They were also significantly longer in C57 lidocaine group than in C57 ischemia group [on the 3rd day of test, (74.1+/-32.7)s vs (49.2+/-19.5)s] (P<0.05). However, they were significantly shorter in apoE lidocaine group than in apoE ischemia group [from the 3rd to the 5th days of test, (40.7+/-27.7)s vs (84.7+/-26.8)s, (31.2+/-19.2)s vs (72.1+/-33.0)s, and (28.0+/-22.1)s vs (60.8+/-26.9)s, respectively] (P<0.05 or 0.01). When compared between two strains, they were significantly longer in apoE ischemia group than in C57 ischemia group (P<0.05 or 0.01). However, they were significantly shorter in apoE lidocaine group than in C57 lidocaine group (P<0.01). (2) The percentages of effective search strategies were significantly lower in the ischemia groups than in the corresponding control groups (P<0.01). They were also significantly lower in C57 lidocaine group than in C57 ischemia group [from the 3rd to the 5th days of test, (18.2+/-11.7)% vs (41.7+/-17.7)%, (22.7+/-20.8)% vs (55.6+/-20.8)%, and (29.6+/-27.0)% vs (66.7+/-21.7)%, respectively] (P<0.01). However, they were significantly higher in apoE lidocaine group than in apoE ischemia group [from the 3rd to the 5th days of test, (41.7+/-25.8)% vs (15.6+/-12.9)%, 8.3+/-20.4)% vs (18.8+/-11.6)%, and (66.7+/-30.3)% vs (28.1+/-20.9)%, respectively] (P<0.01). When compared between two strains, they were significantly lower in apoE ischemia group than in C57 ischemia group (P<0.01). However, they were significantly higher in apoE lidocaine group than in C57 lidocaine group (P<0.01). (3) The parameters of central cholinergic system were significantly lower in the ischemia groups than in the corresponding control groups (P<0.05 or 0.01). They were also significantly lower in C57 lidocaine group than in C57 ischemia group [the activities of AChE of cerebral cortex and hippocampus, (0.44+/-0.09) U/mg protein vs (0.57+/-0.08) U/mg protein, and (0.73+/-0.21) U/mg protein vs (1.08+/-0.27) U/mg protein, respectively; the activities of ChAT of hippocampus, (80.60+/-6.55) pmol/mg protein/min vs (93.66+/-11.15) pmol/mg protein/min; and the binding activities of M receptor of cerebral cortex and hippocampus, (6.03+/-0.74) pmol/mg protein vs (7.49+/-0.48) pmol/mg protein, and (7.56+/-0.92) pmol/mg protein vs (10.65+/-3.35) pmol/mg protein, respectively] (P< 0.05 or 0.01). However, they were significantly higher in ApoE lidocaine group than in ApoE ischemia group [the activities of ChAT of cerebral cortex and hippocampus, (66.99+/-7.55) pmol/mg protein/min vs (46.23+/-4.96) pmol/mg protein/min, and (116.46+/-24.05) pmol/mg protein/min vs (92.08+/-16.33) pmol/mg protein/min, respectively] (P<0.05 or 0.01). When compared between two strains, they were significantly higher in ApoE lidocaine group than in C57 lidocaine group (P< 0.05 or 0.01). CONCLUSION: Transient global cerebral ischemia caused significant brain damages in both strains of mice, which were represented by decline of learning and memorial function and damage of the central cholinergic system. Compared with the C57 mice, the ApoE mice had enhanced susceptibility to global cerebral ischemic injury as shown by more severe decline of the learning and memorial function. In the C57 mice, lidocaine significantly worsened the ischemic brain damage. In the ApoE mice, however, lidocaine significantly alleviated the ischemic cerebral results.
ESTHER : Song_2006_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_38_164
PubMedSearch : Song_2006_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_38_164
PubMedID: 16617359

Title : [Effects of lidocaine on impairment of learning and memory function and cholinergic system caused by cerebral microsphere embolism in rats] - Hua_2005_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_37_616
Author(s) : Hua Z , Wang DX , Wang PY , Zuo PP
Ref : Beijing Da Xue Xue Bao Yi Xue Ban , 37 :616 , 2005
Abstract : OBJECTIVE: To investigate the effects of lidocaine on impairment of learning and memory function and cholinergic system caused by cerebral microsphere embolism in rats.
METHODS: Healthy male Wister rats were randomly divided into the following groups. (1) Control group. (2) 600 microsphere group and 900 microsphere group, in which 600 or 900 microspheres were injected into the right internal carotid artery, respectively. (3) 600 treatment group and 900 treatment group, in which 600 or 900 microspheres were injected into the right internal carotid artery, respectively, and lidocaine was given. Water maze tasks were tested for 5 consecutive days from the 7th postoperative day. The rats were then decapitated and regions of cerebral cortex, hippocampus, and striatum were selected. The activities of choline acetyltransferase and cholinesterase and the binding activity of muscarinic receptor were determined.
RESULTS: (1) The latency periods were significantly longer in the 900 microsphere group than in the control group and in the 600 microsphere group. (2) The percentages of effective search strategy were significantly lower in the 600 and 900 microsphere groups than in the control group. They were significantly higher in the 600 and 900 treatment groups than in the corresponding microsphere groups. (3) The activities of choline acetyltransferase of cerebral cortex were significantly lower in the 900 microsphere and two treatment groups than in the control group. They were also significantly lower in the 600 and 900 treatment groups than in the corresponding microsphere groups. Those of striatum were all significantly lower in the microsphere and treatment groups than in the control group. (4) The activities of cholinesterase of cerebral cortex were significantly lower in the 900 microsphere group than in the control and 600 microsphere groups. They were significantly higher in the 900 treatment group than in the 900 microsphere group. Those of hippocampus were all significantly lower in the microsphere and treatment groups than in the control group. (5) The binding activities of muscarinic receptor of cerebral cortex were significantly lower in the 900 microsphere and two treatment groups than in the control group. They were also significantly lower in the two treatment groups than in the corresponding microsphere groups. Those of hippocampus and striatum were all significantly lower in the microsphere and treatment groups then in the control group. They were also significantly lower in the 600 or 900 treatment group than in the corresponding microsphere group. CONCLUSION: Cerebral microsphere embolism caused significant and quantity-dependent impairment of learning and memory function and cholinergic system in rats. Lidocaine alleviated learning and memory dysfunction caused by cerebral microsphere embolism, but further inhibited the parameters of central cholinergic system.
ESTHER : Hua_2005_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_37_616
PubMedSearch : Hua_2005_Beijing.Da.Xue.Xue.Bao.Yi.Xue.Ban_37_616
PubMedID: 16378114

Title : [3H]benzylpempidine, a new radioligand for probing a putative channel site on nicotinic cholinergic receptors - Wang_1997_Life.Sci_60(13-14)_1271
Author(s) : Wang DX , Sheu SS , Sharma VK , Rubin L , Journet M , Kende AS , Abood LG
Ref : Life Sciences , 60 :1271 , 1997
Abstract : A study was undertaken to assess the receptor binding characteristics of [3H]4-benzylpempidine to an allosteric site on calf brain membranes associated with nicotinic cholinergic receptors and to compare the binding affinity of novel arylpempidine analogs with their ability to antagonize the behavioral effects of nicotine in mice. Scatchard analysis of the binding yielded a K(d) of 20 nM and a B(max) of 330 fmols/mg membrane protein. [3H]4-benzylpempidine appears to be a more satisfactory ligand than [3H]mecamylamine, since it possessed a 50-fold greater affinity and its binding was far less sensitive to inorganic ions and Tris. Among the arylpempidine analogs 4-m-chlorobenzylidenepempidine and 4-benzylidenepempidine had the lowest K(i) values (1.4 nM and 5.0 nM, respectively) and were the most potent in antagonizing nicotine-induced seizures in mice. Although the K(i) values for pempidine and mecamylamine were 1-2 orders of magnitude greater than any of the arylpempidines, the dose required to antagonize nicotine-induced seizures in mice was comparable to the arylpempidines. One explanation for this apparent discrepancy in the correlation of binding affinity and nicotine antagonism is the lower brain penetration of arylpempidines compared to mecamylamine, following their systemic administration to mice.
ESTHER : Wang_1997_Life.Sci_60(13-14)_1271
PubMedSearch : Wang_1997_Life.Sci_60(13-14)_1271
PubMedID: 9096244

Title : Molecular and functional identification of m1 muscarinic acetylcholine receptors in rat ventricular myocytes - Sharma_1996_Circ.Res_79_86
Author(s) : Sharma VK , Colecraft HM , Wang DX , Levey AI , Grigorenko EV , Yeh HH , Sheu SS
Ref : Circulation Research , 79 :86 , 1996
Abstract : The expression of muscarinic acetylcholine receptor (mAChR) subtypes in freshly isolated adult rat ventricular myocytes was investigated by reverse transcription of cellular mRNA followed by amplification of cDNA using the polymerase chain reaction (PCR). After reverse-transcriptase PCR, bands were obtained corresponding to the expected sizes for the m1 and m2 but not for the m3 to m5 mAChRs. The identity of the m1 and m2 bands was confirmed by single-cell PCR, restriction digest mapping, and Southern blot analysis. The presence of m1 and m2, but not m3, mAChR protein in these cells was shown by indirect immunofluorescence studies using subtype-specific antibodies. It was further investigated whether the identified m1 mAChR was responsible for the stimulatory effects on Ca2+ transients by high concentrations of carbachol ( > 10 mumol/L) known to occur in these cells. In pertussis toxin-treated ventricular myocytes electrically stimulated at 1 Hz, carbachol (300 mumol/L) increased the basal Ca2+ level from 96 +/- 7 to 118 +/- 8 nmol/L and the peak Ca2+ transient level from 519 +/- 32 to 640 +/- 36 nmol/L (mean +/- SEM P < .05 for both, n = 8). These effects of carbachol on Ca2+ transients were antagonized by 10 nmol/L pirenzepine, an m1 mAChR-selective antagonist. In contrast, the m2 mAChR-selective antagonist methoctramine (up to 100 nmol/L) did not inhibit the response. These results are the first to use single-cell PCR to probe cardiomyocyte-specific gene expression and indicate that m1 mAChRs are expressed on adult rat ventricular myocytes in addition to m2 mAChRs. The results further suggest that m1 mAChRs mediate the stimulatory responses on Ca2+ transients to high concentrations of cholinergic agonists seen in these cells.
ESTHER : Sharma_1996_Circ.Res_79_86
PubMedSearch : Sharma_1996_Circ.Res_79_86
PubMedID: 8925573

Title : [Experimental research on treatment of acute organophosphorus insecticides poisoning with high-dose atropine: upregulation of muscarinic receptor]. [Chinese] - Si_1994_Zhonghua.Nei.Ke.Za.Zhi_33_583
Author(s) : Si FZ , Wang DX , Yang GQ
Ref : Chinese Journal of Internal Medicine , 33 :583 , 1994
Abstract : Acute organophosphorus insecticides poisoning (AOIP) is a common medical emergency. There is, at present, a tendency to use high-dose atropine treatment (HDAT). This study aims to test if, during AOIP, HDAT would cause upregulation of muscarinic receptor (M-R). Male mice of the same batch and strain were raised, randomly divided into 3 groups and orally fed with DDVP of the same dose. HDAT for 7 days was given to group A, HDAT for 36 hours was given to group B and low-dose atropine treatment for 36 hours was given to group C. Then radionuclide assay was employed to measure the M-R in the brain and atrium of the mice in each group. The results were that, compared with a control group, the Bmax values (fmol.mg protein-1) of M-R in groups A and B were increased significantly (P < 0.01), while that in group C showed no evident change (P > 0.05). These results indicate that HDAT leads to some physiological change in the body, which may be responsible for the development of poisoning rebound and atropine dependence.
ESTHER : Si_1994_Zhonghua.Nei.Ke.Za.Zhi_33_583
PubMedSearch : Si_1994_Zhonghua.Nei.Ke.Za.Zhi_33_583
PubMedID: 7712923

Title : Differences in ligand binding and phosphoinositide turnover between M1 muscarinic receptor gene transfected cells and mouse and rat brain membranes - Wang_1994_Pharmacol.Biochem.Behav_49_405
Author(s) : Wang DX , Lerner-Marmarosh N , Sheu SS , Sharma V , Jou MJ , Abood LG
Ref : Pharmacol Biochem Behav , 49 :405 , 1994
Abstract : The present study describes some unexpected receptor mediated effects of N-methylcarbamylcholine on mouse M1 muscarinic receptor gene transfected cell line (M1Y1) that were not evident from biochemical studies with mouse and rat brain tissue where N-methylcarbamylcholine exhibited only nicotinic properties. Although N-methylcarbamycholine was devoid of muscarinic properties in mouse and rat brain preparations, as determined by phosphoinositide turnover and inhibition of [3H]QNB binding, it exhibited significant muscarinic characteristics in the transfected M1Y1 cell line. At a concentration of 10(-6) M or greater, N-methylcarbamycholine caused a transient increase in intracellular Ca2+ of 50 s duration that was reversible by atropine or pirezepine. The Ca(2+)-transient was not elicited by other nicotinic agents such as nicotine and N,N-dimethylcarbamylcholine, a close analogue of N-methylcarbamylcholine, with comparable affinity for nicotinic receptors and devoid of muscarinic activity. N-Methylcarbamylcholine also stimulated phosphoinositide turnover in M1Y1 cells with an estimated EC50 value 10 times greater than that of carbachol, and the effect was blocked by atropine. Both carbachol and N-methylcarbamycholine inhibited [3H]QNB binding in a concentration-dependent manner; however, the IC50 for carbachol was over two orders of magnitude greater than that observed in mouse and rat brain membranes. In considering possible explanations for the differential characteristics of N-methylcarbamylcholine in mouse and rat brain as compared to the transfected M1Y1 cells, it was concluded that the difference may be attributable to differences in the receptor-transduction coupling efficiency and the microenvironment of the muscarinic receptors.
ESTHER : Wang_1994_Pharmacol.Biochem.Behav_49_405
PubMedSearch : Wang_1994_Pharmacol.Biochem.Behav_49_405
PubMedID: 7824557