Evidence for two different P2-purinoceptors on beta cell and pancreatic vascular bed.

1 The effects of a 2-substituted analogue of adenosine 5'-triphosphate (ATP), 2-methylthioadenosine triphosphate (2-methylthio ATP) have been studied on insulin secretion and flow rate of the isolated pancreas of the rat, perfused in the presence of glucose (8.3 mM). 2 2-Methylthio ATP (16.5-1650 nM) increased insulin secretion in a biphasic and concentration-dependent manner; the kinetics were comparable to those previously obtained with ATP. A comparison of relative potency between ATP and 2-methylthio ATP showed that 2-methylthio ATP was 45 times more potent than ATP. 3 2-Methylthio ATP also provoked a transient decrease of the flow rate in a concentration-dependent manner but at concentrations (165-825 microM) about 1000 fold higher than those needed to increase insulin secretion. A comparison of relative potency between the natural derivative and 2-methylthio ATP showed that 2-methylthio ATP was only twice as potent as ATP. 4 These and other previous results (with phosphate-modified analogues of ATP) provide evidence for two different types of P2-purinoceptors on endocrine cell and vessel cells of the pancreas. A P2Y subtype, mediating an increase of insulin secretion, is present on the beta cell of the pancreas. A P2X subtype, mediating vasoconstriction, is present on the vascular bed of the rat pancreas.