Roles of ATP sensitive potassium channel in modulating gastric tone and accommodation in dogs

Abstract

Objective: The ATP sensitive potassium (KATP) channel plays an important role in the regulation of resting membrane potential and membrane excitability. The role of the KATP channel in modulating gastric motility is unclear. The aim of this study was to investigate the role and mechanism of the KATP channel in modulating gastric tone and accommodation in dogs.Materials and methods: Gastric volume under a constant pressure reflecting gastric tone was measured using a barostat device in dogs equipped with a gastric cannula. Gastric accommodation was evaluated by the difference in gastric volume before and after a liquid meal. The roles of cholinergic and nitrergic pathways in the inhibitory effect of pinacidil (a KATP opener) were assessed.Results: 1) Pinacidil dose-dependently decreased gastric tone at a dosage of 30 (p = 0.628), 100 (p = 0.013) and 300 μg kg−1 (p < 0.001). 2) Glibenclamide, a KATP blocker, completely blocked the inhibitory effect of pinacidil on gastric tone. 3) Atropine did not block the inhibitory effect of pinacidil on gastric tone but Nω-Nitro-L-arginine methyl ester markedly attenuated the inhibitory effect of pinacidil (p = 0.004). 4) Glibenclamide significantly reduced gastric accommodation (p < 0.001) while pinacidil had no effects on gastric accommodation. 5) Glibenclamide significantly reduced nitric oxide donor sodium nitroprusside-induced gastric relaxation.Conclusions: These findings indicate that the KATP channel plays an important role in modulating gastric tone and accommodation in dogs. The inhibitory effect of pinacidil on gastric tone was through the nitrergic pathway as well as acting directly on smooth muscle cells.