BRITISH JOURNAL OF PHARMACOLOGY Volume177, Issue14 July 2020 Pages 3258-3272

Source of dopamine in gastric juice and luminal dopamine‐induced duodenal bicarbonate secretion via apical dopamine D2 receptors

Xiao‐Yan FengJing‐Ting YanGuang‐Wen LiJing‐Hua LiuRui‐Fang FanShi‐Chao LiLi‐Fei ZhengYue ZhangJin‐Xia Zhu

Abstract

Background and Purpose

Dopamine protects the duodenal mucosa. Here we have investigated the source of dopamine in gastric juice and the mechanism underlying the effects of luminal dopamine on duodenal bicarbonate secretion (DBS) in rodents.

Experimental Approach

Immunofluorescence, UPLC‐MS/MS, gastric incubation and perfusion were used to detect gastric‐derived dopamine. Immunofluorescence and RT‐PCR were used to examine the expression of dopamine receptors in the duodenal mucosa. Real‐time pH titration and pHi measurement were performed to investigate DBS.

Key Results

H+‐K+‐ATPase was co‐localized with tyrosine hydroxylase and dopamine transporters in gastric parietal cells. Dopamine was increased in in vivo gastric perfusate after intravenous infusion of histamine and in gastric mucosa incubated, in vitro, with bethanechol chloride or tyrosine. D2 receptors were the most abundant dopamine receptors in rat duodenum, mainly distributed on the apical membrane of epithelial cells. Luminal dopamine increased DBS in a concentration‐dependent manner, an effect mimicked by a D2 receptor agonist quinpirole and inhibited by the D2 receptor antagonist L741,626, in vivo D2 receptor siRNA and in D2 receptor −/− mice. Dopamine and quinpirole raised the duodenal enterocyte pHi. Quinpirole‐evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA‐AM or in D2 receptor−/− mice.

Conclusion and Implications

Dopamine in the gastric juice is derived from parietal cells and is secreted along with gastric acid. On arrival in the duodenal lumen, dopamine increased DBS via an apical D2 receptor‐ and calcium‐dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa.

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