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Rutaecarpine induces chloride secretion across rat isolated distal colon

文献类型:期刊论文

作者Wu, DaZheng; Hu, Zhibi
刊名The Journal of pharmacology and experimental therapeutics
出版日期2008-04
卷号325期号:1页码:256-66
ISSN号1521-0103
DOI10.1124/jpet.107.131961
文献子类Article
英文摘要The present study evaluated the effect of rutaecarpine (Rut) on Cl(-) secretion across rat distal colonic mucosa. Basolateral application of Rut elicited an increase in short-circuit current (I(SC)) response in a concentration-dependent manner. Evidence that Rut-stimulated I(SC) was due to Cl(-) secretion is based on 1) inhibition of current by bumetanide; 2) Cl(-) channel blockers diphenylamine-2-carboxylate, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, and glibenclamide; and 3) removal of Cl(-) ions in bath solution. Determination of neurogenic blockers on Rut-induced I(SC) indicated that pretreatment of tissues with tetrodotoxin or indomethacin, but not atropine or hexamethonium, inhibited Rut-induced response. Treatment with Rut led to release and synthesis of prostaglandin E(2) in rat colonic mucosa. Rut-stimulated I(SC) was markedly reduced by pretreatment with MDL-12,330A [cis-N-[2-phenylcyclopentyl]-azacyclotridec-1-en-2-amine] and N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), but not with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, bisindolylmaleimide, and thapsigargin. Elimination of the extracellular Ca(2+) also did not alter Rut response. Rut treatment resulted in the increase in intracellular cAMP levels and the activation of protein kinase A. Depolarizing the basolateral membrane with high K(+) showed that Rut-stimulated apical Cl(-) current was largely prevented by cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors. Permeabilizing apical membrane with nystatin revealed that Rut-stimulated basolateral K(+) current was specifically inhibited by Ba(2+) ions and chromanol 293B. The evidence derived from present study suggests that Rut-stimulated Cl(-) secretion is mediated by generation of endogenous prostaglandin E(2) and that it also involves the stimulation of cAMP and protein kinase A pathways, which subsequently lead to the activation of apical Cl(-) channels, mostly the CFTR and basolateral cAMP-dependent K(+) channels.
语种英语
源URL[http://119.78.100.183/handle/2S10ELR8/266537]  
专题中国科学院上海药物研究所
通讯作者Wu, DaZheng
作者单位Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd., Zhangjiang Hi-tech Park, Shanghai 201203, People's Republic of China
推荐引用方式
GB/T 7714
Wu, DaZheng,Hu, Zhibi. Rutaecarpine induces chloride secretion across rat isolated distal colon[J]. The Journal of pharmacology and experimental therapeutics,2008,325(1):256-66.
APA Wu, DaZheng,&Hu, Zhibi.(2008).Rutaecarpine induces chloride secretion across rat isolated distal colon.The Journal of pharmacology and experimental therapeutics,325(1),256-66.
MLA Wu, DaZheng,et al."Rutaecarpine induces chloride secretion across rat isolated distal colon".The Journal of pharmacology and experimental therapeutics 325.1(2008):256-66.

入库方式: OAI收割

来源:上海药物研究所

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