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

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 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.

Reduced acetylcholine and elevated muscarinic receptor 2 in duodenal mucosa contribute to the impairment of mucus secretion in 6-hydroxydopamine-induced Parkinson’s disease rats

“…The methods used for western blotting have previously been described in detail (Feng et al 2020). Briefly, homogenized rat duodenal mucosa was lysed in sodium dodecyl sulfate lysis buffer containing proteinase and phosphatase inhibitors.…”

Dopamine regulates colonic glial cell‐derived neurotrophic factor secretion through cholinergic dependent and independent pathways

“…Bush et al have found that the ablation of EGCs, which are the source of GDNF, leads to dysfunction of the intestinal epithelial barrier and spontaneous jejuno‐ileitis (Bush et al, 1998). Besides, DA has attracted increasing attention owing to its significant contribution to several GI functions, such as intestinal motility, mucus secretion, ion transport and mucosal barrier (Feng et al, 2020, 2017; Li et al, 2019; Zhang et al, 2021). Several studies have reported that the D 1 receptor promotes GDNF release from human astrocytes (Kinor et al, 2001; Kuric et al, 2013).…”

“…Our previous studies have shown that dopamine receptors are widely present in the mucosa and smooth muscle, and the ENS of GI tract (Feng et al, 2020; Li et al, 2019; Zhang et al, 2012, 2015). DA modulates GI mucosal barrier function and motility via dopamine receptors (Feng et al, 2020, 2017; Li et al, 2006; Zhang et al, 2015). Previous studies have reported that the D 2 receptor is involved in the suppression of ACh release from enteric neurons (Palma & Kaufmann, 2018).…”

“…DA is a key neurotransmitter in both the brain and gut. Our previous studies have shown that dopamine receptors are widely present in the mucosa and smooth muscle, and the ENS of GI tract (Feng et al, 2020; Li et al, 2019; Zhang et al, 2012, 2015). DA modulates GI mucosal barrier function and motility via dopamine receptors (Feng et al, 2020, 2017; Li et al, 2006; Zhang et al, 2015).…”

Pancreatic acinar cells utilize tyrosine to synthesize L-dihydroxyphenylalanine

“…Besides, L-DOPA in pancreatic juice can also be transported to the intestine and utilized by the enteric nervous system 30 or intestinal bacteria 31 to synthesize DA, where DA plays a variety of regulatory roles. [32][33][34] The discovery of L-DOPA synthesis in pancreatic acinar cells may be more conducive to providing the precursor for pancreatic and intestinal DA synthesis.…”