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Source of dopamine in gastric juice and luminal dopamine‐induced duodenal bicarbonate secretion via apical dopamine D 2 receptors
Author(s) -
Feng XiaoYan,
Yan JingTing,
Li GuangWen,
Liu JingHua,
Fan RuiFang,
Li ShiChao,
Zheng LiFei,
Zhang Yue,
Zhu JinXia
Publication year - 2020
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15047
Subject(s) - dopamine , endocrinology , medicine , chemistry , dopamine receptor , dopamine receptor d2 , gastric acid , biology , secretion
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 pH i 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. D 2 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 D 2 receptor agonist quinpirole and inhibited by the D 2 receptor antagonist L741,626, in vivo D 2 receptor siRNA and in D 2 receptor −/− mice. Dopamine and quinpirole raised the duodenal enterocyte pH i . Quinpirole‐evoked DBS and PI3K/Akt activity were inhibited by calcium chelator BAPTA‐AM or in D 2 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 D 2 receptor‐ and calcium‐dependent pathway. Our data provide novel insights into the protective effects of dopamine on the duodenal mucosa.