Differential expression of motilin receptors on the endothelium of dog gastrointestinal arteries and motilin-induced motilin receptor dependent relaxation of corresponding arteries

Peptides. 2021 Sep:143:170574. doi: 10.1016/j.peptides.2021.170574. Epub 2021 May 31.

Abstract

Background: Motilin's role in the regulation of vascular tone and hemodynamic besides gastrointestinal motility is concerned. This study aimed to investigate the expression of motilin receptors in gastrointestinal arteries and motilin-induced relaxation.

Material and methods: The expression of motilin receptors in the left gastric artery (LGA), superior mesenteric artery (SMA), and inferior mesenteric artery (IMA) of adult dogs (1.5-5 years old) were analyzed by immunochemistry, RT-PCR, and western blotting. Motilin's effects on the gastrointestinal arteries were evaluated in a multi-wire myograph system.

Results: Immunohistochemical staining showed that motilin receptor was expressed on the membranes of endothelial cells with the fluorescence intensity LGA > SMA > IMA (P < 0.01). The motilin receptor's mRNA and protein expression levels shared the same distribution patterns as it in fluorescence intensity (P < 0.01). In isolated LGA preparations precontracted with U46619 (a thromboxaneA2 analog), motilin induced a concentration-dependent relaxation, and the EC50 was 8.8 × 10-8 ± 0.9 × 10-8 M. Motilin-induced relaxation on the three arteries also shared the same pattern as it in fluorescence intensity (P < 0.01) and inhibited by denuded-endothelium and GM-109 (a motilin receptor antagonist) but not by atropine (a muscarinic receptor antagonist).

Conclusions: Motilin receptors are expressed differentially on the membranes of endothelial cells in dog gastrointestinal arteries with a significantly high expression in the LGA. Motilin-induced relaxation is endothelium- and motilin receptor-dependent. The motilin receptor expressed on the endothelial cell membrane of the LGA is the molecular basis for motilin regulating gastric blood flow under physiological conditions in dogs.

Keywords: Artery relaxation; Endothelium; Gastrointestinal arteries; Motilin receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteries / metabolism*
  • Dogs
  • Endothelium, Vascular / metabolism*
  • Female
  • Gastrointestinal Tract / blood supply
  • Gene Expression Regulation
  • Male
  • Motilin / metabolism*
  • Receptors, Gastrointestinal Hormone / genetics*
  • Receptors, Gastrointestinal Hormone / metabolism
  • Receptors, Neuropeptide / genetics*
  • Receptors, Neuropeptide / metabolism

Substances

  • Receptors, Gastrointestinal Hormone
  • Receptors, Neuropeptide
  • motilin receptor
  • Motilin