Stimulation by nizatidine,a histamine H_2-receptor antagonist,of duodenal HCO_3^-secretion in rats:relation to anti-cholinesterase activity  

作　　者：Koji Takeuchi Shoji Kawauchi Hideo Araki Shigeru Ueki Osamu Furukawa 

机构地区：[1]Department of Pharmacology and Experimental Therapeutics,Kyoto Pharmaceutical University,Misasagi,Yamashina,Kyoto 607-8414,Japan [2]CURE,Bldg.114,Suite 217 West LA VAMC 11301 Wilshire Blvd.Los Angeles,CA 90073

出　　处：《World Journal of Gastroenterology》2000年第5期651-658,共8页世界胃肠病学杂志（英文版）

摘　　要：AIM To examine whether nizatidine stimulates duodenal HCO_3^- secretion in rats by inhibiting AChE activity. METHODS Under pentobarbital anesthesia,a proximal duodenal loop was perfused with saline,and the HCO_3 secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCI.Nizatidine,neostigmine,carbachol or famotidine was administered i.v.as a single injection. RESULTS Intravenous administration of nizatidine(3-30 mg/kg)dose-dependently increased duodenal HCO_3^- secretion,and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg.This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility,mimicked by i.v.injection of neostigmine(0.03 mg/kg),and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin,a cyclooxygenase inhibitor,or N^G-nitro-L-arginine methyl ester,a NO synthase inhibitor.The HCO_3^- secretory response to acetylcholine(0.001 mg/kg)was significantly potentiated by the concurrent administration of nizatidine(3mg/kg,i.v.).The IC_(50)of nizatidine for AChE of rat erythrocytes was 1.4×10^(-6)M,about 12 times higher than that of neostigmine.Neither famotidine(>10^(-3)M, 30mg/kg,i.v.)nor cisapride(> 10^(-3)M, 3mg/kg,i.v.)had any influence on AChE activity or duodenal HCO_3^- secretion.Duodenal damage induced by acid perfusion(100 mM HCI for 4 h)in the presence of indomethacin was significantly prevented by nizatidine and neostigmine,at the doses that increased the HCO_3^- secretion. CONCLUSION Nizatidine stimulates duodenal HCO_3^- secretion,in both vagal-dependent and atropine-sensitive manners,and the action is associated with the anti-AChE activity of this agent.AIM To examine whether nizatidine stimulatesduodenal HCO₃^- secretion in rats by inhibitingAChE activity.METHODS Under pentobarbital anesthesia,aproximal duodenal loop was perfused withsaline,and the HCO₃ secretion was measuredat pH 7.0 using a pH-stat method and by adding10mM HCI.Nizatidine,neostigmine,carbacholor famotidine was administered i.v.as a singleinjection.RESULTS Intravenous administration ofnizatidine（3-30 mg/kg）dose-dependentlyincreased duodenal HCO₃^- secretion,and theeffect at 10mg/kg was equivalent to thatobtained by carbachol at 0.01 mg/kg.Thisnizatidine action was observed at the same doserange that inhibited acid secretion and enhancedgastric motility,mimicked by i.v.injection ofneostigmine（0.03 mg/kg）,and significantlyattenuated by bilateral vagotomy and prior s.c.administration of atropine but not byindomethacin,a cyclooxygenase inhibitor,orN^G-nitro-L-arginine methyl ester,a NO synthaseinhibitor.The HCO₃^- secretory response toacetylcholine（0.001 mg/kg）was significantlypotentiated by the concurrent administration ofnizatidine（3mg/kg,i.v.）.The IC₅₀of nizatidine for AChE of rat erythrocytes was1.4×10^-6M,about 12 times higher than that ofneostigmine.Neither famotidine(>10^-3M,30mg/kg,i.v.)nor cisapride(> 10^-3M,3mg/kg,i.v.)had any influence on AChEactivity or duodenal HCO₃^- secretion.Duodenaldamage induced by acid perfusion（100 mM HCIfor 4 h）in the presence of indomethacin wassignificantly prevented by nizatidine andneostigmine,at the doses that increased theHCO₃^- secretion.CONCLUSION Nizatidine stimulates duodenalHCO₃^- secretion,in both vagal-dependent andatropine-sensitive manners,and the action isassociated with the anti-AChE activity of thisagent.

关 键 词：NIZATIDINE histamine H_2 receptor blockaders duodenal HCO_3^-secretion cholinesterase inhibitors RATS 

分 类 号：R574[医药卫生—消化系统]