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《中国生理学会第24届全国会员代表大会暨生理学学术大会论文汇编》2014年
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Regulation of Gastric-derived Dopamine on Duodenal Epithelial Ion Transport in Rats

冯小燕  朱进霞  
【摘要】:Background and Aims:Gastric epithelial cells are able to synthesize dopamine(DA),which plays an important role in the gastrointestinal mucosa protection.However,the mechanism is largely unknown.The present study aims to investigate the mechanism underlying the effect of gastric-derived DA and DA receptors on the duodenal epithelial ion transport in rats.Methods:In vivo gastric perfusion,radioimmunoassay,ultra pressure liquid chromatography-mass spectrometry,immunofluorescence,short-circuit current(ISC),real-time p H titration,p H-sensitive fluorescent probes(BCECF-AM)and human D5 receptor transgenic mice were used in the present studies.Results:Immunofluorescence showed that the DAT-immunoreactivity(IR)was remarkably distributed in the H+-K+-ATPase-IR mucosal cells in rat gastric corpus,suggesting the parietal cells are dopaminergic.Intravenous infusion of histamine(2mg/kg/h,n=9,p0.05)or decreasing gastric p H(p H=2.5,n=5,p0.01)significantly increased DA content in the gastric perfusate by 53.2%and 33.5%,respectively.Basolateral DAdose-dependently inhibited ISC(IC50 was 5.34μmol/l)without alterations of duodenal bicarbonate secretion(DBS)or apical p H(n=7),which was mimicked by D1 agonist SKF38393 and blocked by D1antagonist SCH-23390.DA-induced change in ISC(ISC)was accordant with the D5 expressions in human D5 transgenic mice,from-3.03±0.57(control)to-4.44±0.86(up,n=8,p0.05)and-2.24±0.64μA/cm2(down,n=8,p0.01).However,apical DA did not affect ISC,but significantly increased DBS(0.001-10μmol/l)with an apparent EC50 of 4.15μmol/l(n=7).Apical DA-induced DBS was mimicked by apical D2 agonist quinpirode and completely inhibited by D2 antagonist sulpiride and L741,626.By mean of BCECF-AM,DA or quinpirode-induced DBS was further confirmed by the enhanced duodenal fluorescence intensity.The immunofluorescence of DA receptors(D1~D5)were distributed in the duodenal epithelia with clear D5-IR(i.e.D1b)at both apical and basolatoral membranes,and D2-IR(including D2,D3,D4)at the apical membrane in Brunner's glands and duodenal crypts.Conclusions:DA increases DBS through apical D2 and duodenal ion transport without DBS through D5.This study reveals an unreported effect of gastric-derived DA on DBS,and provides a new insight on the modulation of DA on the duodenal mucosa protection.

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