Dopamine promotes colonic mucus secretion through dopamine D₅ receptor in rats

Abstract

Dopamine regulates gastrointestinal mucosal barrier. Mucus plays important roles in the protection of intestinal mucosa. Here, the regulatory effect of dopamine on rat colonic mucus secretion was investigated. RT-PCR, immunofluorescence, Periodic Acid-Schiff reagent assay, Alcian blue-Periodic Acid-Schiff staining, and enzyme-linked immunosorbent assay were used to observe the expression of dopamine receptor and the direct effect of dopamine on the colonic mucus. Mice injected intraperitoneally with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) destroying enteric dopamine (DA) neurons, rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra damaging central dopaminergic neurons, and dopamine D5 receptor-downregulated transgenic mice were used to detect the effect of endogenous enteric dopamine or dopamine receptors on distal colonic mucus. Our results indicated that D5 immunoreactivity was widely distributed on the colonic goblet cells. Dopamine dose-dependently increased rat distal colonic mucus secretion in vitro. D1-like receptor antagonist SCH23390 inhibited dopamine (1 μΜ)-induced distal colonic mucus secretion. D1-like receptor agonist SKF38393 promoted mucin 2 (MUC2) secretion and increased the intracellular cAMP level of colonic mucosa. D5 receptor-downregulated transgenic mice showed a decreased colonic MUC2 content. MPTP-treated mice exhibited lower colonic dopamine content and decreased colonic mucus content. 6-OHDA rats had an increase in the dopamine content in colonic mucosa but decreases in the protein levels of D1 and D5 receptors and MUC2 content in the colonic mucosa. These findings reveal that dopamine is able to promote distal colonic mucus secretion through the D5 receptor, which provides important evidence to better understand the possible role of dopamine in the colonic mucosal barrier.

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.…”

Biogenic Amines: Signals Between Commensal Microbiota and Gut Physiology

“…In humans, RT-PCR analysis showed that β1 and β2 adrenergic receptors are present in the colon mucosa (60). Regarding dopamine receptors, their subtypes were confirmed in rat colonic epithelia (61) and goblet cells (62). Moreover, an excellent report using an advanced single-cell RNA sequencing technique recently demonstrated that Tuft cells express dopamine receptor D3 genes (63).…”

Gut Microbiota-Derived Metabolites in Irritable Bowel Syndrome

“…The dopamine D2 receptor antagonist has been applied to treat IBS patients to improve gastrointestinal motility ( Tack et al., 2006 ). The dopamine D5 receptor may play an important role in increasing the permeability of duodenal epithelial cells and protecting the colonic mucosa ( Li et al., 2019 ). Moreover, several bacterial strains are highly correlated with alterations of dopaminergic pathways for growth and metabolism, including E. coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Shigella sonnei , and Staphylococcus aureus ( Strandwitz, 2018 ).…”