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

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.

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