INTERACTIONS OF ISLET HORMONES WITH ACETYLCHOLINE IN THE ISOLATED RATPANCREAS

This study investigates the effects of the islet hormones, insulin (IN S), glucagon (GLU) and somatostatin (SOM) on acetylcholine (ACh)-evoke d amylase secretion and calcium (Ca2+) mobilization in the isolated ra t pancreas. Stimulation of pancreatic segments and acini with either I NS, GLU or SOM resulted in small increases of amylase output compared to much large increases in enzyme output with ACh. Combinations of the peptide hormones with ACh resulted in enhanced secretory responses co mpared to the effects obtained with either ACh or each of the islet ho rmone alone. Genistein, the tyrosine kinase inhibitor, evoked a decrea se in amylase output from pancreatic segments. It had no effect on the ACh-evoked secretory response but it markedly inhibited the potentiat ion of the islet hormones with ACh. In pancreatic acinar cells either INS, GLU or SOM elicited moderate increases in amylase output compared to much larger responses with ACh. Furthermore, the islet hormones fa iled to potentiate the secretory effect of ACh in pancreatic acini. In fura-2 AM loaded acinar cells both INS and GLU evoked small increases in intracellular free calcium concentration [Ca2+](i) compared to a m uch larger elevation with ACh. Both INS and GLU enhanced the ACh-evoke d [Ca2+](i). Genistein elicited a decrease in [Ca2+](i) both in the ab sence and presence of both INS and GLU. It also decreased the rise in [Ca2+](i) resulting from the combined presence of ACh with both INS an d GLU. SOM had no significant effect on the ACh-induced [Ca2+](i). Whe n genistein was combined with ACh and SOM there was a decrease in [Ca2 +](i) compared to the response obtained with SOM and ACh alone. The re sults indicate that both tyrosine kinase and cellular Ca2+ seem to be the intracellular mediators associated with the enhanced secretory res ponses obtained with a combination of the islet hormones with ACh. Fin ally, our results using immunohistochemical techniques confirm the pre sence of INS-, GLU-SOM-and ACh-immunoreactive cells in the endocrine a nd neural elements of the rat pancreas. (C) 1997 Elsevier Science Inc.