A Reciprocal Regulation of Ca2+-Activated K+ Channel by Insulin and Somatostatin in Guinea-Pig Pancreatic Acinar Cells.

Abstract

The pancreatic acini are in close contact with the surrounding islets, having no significant fibrous capsules, and receptors of insulin [1][2][3][4] and somatostatin [5,6] on the pancreatic acinar cell have been reported. Therefore, this might eventually enter into very close interrelation between the exocrine pancreas and the endocrine islet of Langerhans.The secretion of the pancreatic acinar cells has for a long time been thought to be regulated by the islet hormones [7], but few detailed studies indicate hormonal regulation of the acinar cells. In digestive enzyme secretion, for example, insulin potentiates acetylcholine-induced [8,9] and, cholecytokinin-induced amylase secretion [10]. In vivo, somatostatin inhibits both Ca 2ϩ -induced and cyclic AMP-induced amylase secretion [11][12][13][14], but in vitro, a few consistent effects on secretion have been described [13,15]. As for ionic fluid secretion from pancreatic acini, only one report concerns the effect of insulin on cation channel [16].Ca 2ϩ -activated K ϩ channels, which have been suggested to regulate the K ϩ permeability changes in plasma membrane during fluid secretion, have been identified on the basolateral membrane of Cl Ϫ -secreting pancreatic acinar cells in a variety of animal species [17][18][19][20]. It has been suggested that these K ϩ channels are important for Cl Ϫ uptake into cells [21]. Secretagogues evoking an increase in cytoplasmic Ca 2ϩ level activate K ϩ channels causing an increase in the local external K ϩ concentration. Na ϩ , K ϩ , and Cl Key words: insulin, somatostatin, potassium channels, pancreatic juice, cyclic AMP. Abstract:The effects of islet hormones, insulin and somatostatin, on the regulation of the opening of Ca 2ϩ -activated K ϩ 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 ϩ channel. The open-state probability (p) of K ϩ 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 ϩ channel, which was reversed by an application of somatostatin (Tyr-somatostatin 28). The addition of ACh followed by forskolin or dibutyryl adenosine 3Ј,5Ј-cyclic monophosphate (dbcAMP) to the bath solution evoked an increase in the p value of K ϩ 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 2ϩ -activated K ϩ channel through a cyclic AMP-dependent signaling pathway.