Source of dopamine in gastric juice and luminal dopamine‐induced duodenal bicarbonate secretion via apical dopamine receptor 2

BACKGROUND AND PURPOSE: Dopamine (DA) can protect the duodenal mucosa. The aim of the present study was to investigate the source of DA in gastric juice and the mechanism underlying the effects of luminal DA on duodenal bicarbonate secretion (DBS) in rodents. EXPERIMENTAL APPROACH: Immunofluorescence, UPLC-MS/MS, gastric incubation and perfusion were used to detect gastric-derived DA. Immunofluorescence and RT-PCR were used to examine the expression of DA receptors (DARs) 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 DA transporters in gastric parietal cells. DA was increased in in vivo gastric perfusate after intravenous infusion of histamine and in in vitro gastric mucosa incubated with bethanechol chloride or tyrosine. D2 R was the most abundant DAR in rat duodenum and mainly distributed on the apical membrane of epithelial cells. Luminal DA increased DBS in a concentration-dependent manner, which was mimicked by D2 R agonist quinpirole and inhibited by D2 R antagonist L741,626, in vivo D2 R siRNA and in D2 R(-/-) mice. DA and quinpirole enhanced the duodenal enterocyte pHi . Quinpirole-evoked DBS and PI3K/Akt activity were significantly inhibited by calcium chelator BAPTA-AM or in D2 R(-/-) mice. CONCLUSION AND IMPLICATIONS: DA in the gastric juice is derived from parietal cells and is secreted along with gastric acid. When it arrives at the duodenal lumen, DA increases DBS via an apical D2 R- and calcium-dependent pathway. The present study provides novel insight into the protective effects of DA on the duodenal mucosa.