Inhibitory effect of somatostatin on secretin-induced augmentation of the slowly activating K+ current (IKs) in the rat pancreatic acinar cell.

Recently, the slowly-activating voltage-dependent K+ channel current (IKs) has been reported in the rat pancreatic acinus (RPA). IKs is modulated positively by ACh and secretin, Ca2+ - and cAMP-mediated secretagogues, respectively. In this study, we investigated the effect of somatostatin (SS), a well-known inhibitory hormone of pancreatic fluid secretion, on I(Ks) in RPAs. The whole-cell patch clamp technique was applied to intact RPAs. Step-like depolarizations from -60 mV to above -40 mV induced IKs, a response blocked by the chromanols 293B [concentration for half-maximal inhibition (IC50) 5.3 microM), HMR-1556 (IC50 0.17 microM) and IKs 420 (IC50 2 nM). The application of secretin (5 nM), forskolin (5 microM) or 8-Br-cAMP (0.3 mM) increased the amplitude of IKs two- to fourfold. The addition of SS (1-100 nM) markedly suppressed the augmentation of IKs by secretin or forskolin but had no effect on IKs stimulated by 8-Br-cAMP, nor did SS block the Ca2+ -mediated augmentation of IKs by ACh. These results suggest that the effect of SS on IKs in the rat pancreatic acinar cell is mediated by inhibition of cAMP production, which may play a role in the negative regulation of the exocrine pancreas by SS.