The effect of ghrelin O-acyltransferase inhibitor on gastric H+-K+-ATPase activity and GOAT/ghrelin system in gastric mucosal cells in vitro

Gen Comp Endocrinol. 2018 Oct 1:267:167-171. doi: 10.1016/j.ygcen.2018.06.020. Epub 2018 Jun 30.

Abstract

Ghrelin is implicated in the regulation of gastric functional development. The octanoylation of ghrelin is critical for its physiological functions which dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. To investigate the effect of GOAT on gastric acid secretion and expression of ghrelin in vitro. Primary cultures of gastric mucosal cells were challenged with 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (The GOAT inhibitor), respectively, for 24 h in order to further clarify the effect of GOAT on H+-K+-ATPase activity. In vitro, GO-CoA-Tat significantly increased ghrelin and GOAT mRNA expression at 1.5 × 10-5, 1.5 × 10-4 and 1.5 × 10-3 mol/mL, and augmented cell total ghrelin secretion at 1.5 × 10-3 mol/mL. But cell acylated ghrelin secretion was reduced at 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). And cell acylated ghrelin synthesis was reduced at 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). In accordance with acylated ghrelin level, H+-K+-ATPase activity were decreased with 1.5 × 10-4 and 1.5 × 10-3 mol/mL GO-CoA-Tat (P < 0.05). These results indicated that GOAT inhibitor decreases the acylated ghrelin level and H+-K+-ATPase activity in vitro.

Keywords: Acylated ghrelin; GOAT; H(+)–K(+)-ATPase activity; Total ghrelin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / antagonists & inhibitors*
  • Acyltransferases / genetics
  • Acyltransferases / metabolism
  • Animals
  • Cell Line
  • Culture Media
  • Enzyme Inhibitors / pharmacology*
  • Gastric Mucosa / cytology*
  • Gastric Mucosa / enzymology*
  • Ghrelin / metabolism*
  • H(+)-K(+)-Exchanging ATPase / metabolism*
  • Membrane Proteins
  • Mice
  • Peptides / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Culture Media
  • Enzyme Inhibitors
  • GO-CoA-Tat
  • Ghrelin
  • Membrane Proteins
  • Peptides
  • RNA, Messenger
  • Acyltransferases
  • Mboat4 protein, mouse
  • H(+)-K(+)-Exchanging ATPase