P 2 purinoceptor agonists stimulate somatostatin secretion from dog pancreas

Abstract

The effects of ATP and ADP structural analogues (2-methylthio ATP; α,ß-methylene ADP) on somatostatin secretion were tested in dogs. Insulin and glucagon secretion was also evaluated. Our experiments were performed in vivo and vitro. In vivo, 2-methylthio ATP was infused directly into the pancreaticoduodenal artery of anesthetized dogs and blood was sampled from the pancreaticoduodenal vein. This ATP analogue (≈ 15 μM) immediately induced stimulation of both somatostatin and insulin secretion, which was accompanied by a slight reduction of glycemia. A delayed increase in glucagon output was observed. In vitro, using the isolated perfused dog pancreas uncinate process, α,ß-methylene ADP, a stable ADP analogue (16.5 μM), was infused in the presence of a substimulating glucose concentration (4.2 mM). Under these conditions, α,ß-methylene ADP immediately induced the stimulation of somatostatin secretion without affecting basal insulin and glucagon secretion. In conclusion our results suggest the presence of P 2 purinoceptors on pancreatic somatostatin secreting cells.