A reciprocal regulation of Ca(2+)-activated K(+) channel by insulin and somatostatin in guinea-pig pancreatic acinar cells

The effects of islet Hormones, Insulin and somatostatin, on the regulation of the opening of CA(2+)-activated K(+) channels in the basolateral plasma membrane of primary cultured pancreatic acinar cells of guinea-pig were studied by cell-attached single-channel recording technique. A single application of Insulin or somatostatin did not influence the opening of K(+) channel. The open-state probability (p) of K(+) channel induced by the application of acetylcholine (ACh) to the bath solution was increased by Insulin in the presence of ACh. The enhancement effect of Insulin on the increased frequency of the channel opening was not seen when concomitantly applied with protein kinase A inhibitor, Rp-cAMPS triethylamine. Insulin increased the p value of K(+) channel, which was reversed by an application of somatostatin (Tyr-somatostatin 28). The addition of ACh followed by forskolin or dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) to the bath solution evoked an increase in the p value of K(+) channel. After increasing the channel opening, the addition of somatostatin reduced the p value, but not with dbcAMP. Taken together, the results suggest that Insulin and somatostatin reciprocally modify the ACh-induced opening of the CA(2+)-activated K(+) channel through a cyclic AMP-dependent signaling pathway.