Evidence for two different P2‐purinoceptors on β cell and pancreatic vascular bed

Abstract

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 that ATP. 3 2‐Methylthio ATP also provoked a transient decrease of the flow rate in a concentration‐dependent manner but at concentrations (165–825 μm) 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 P_2Y subtype, mediating an increase of insulin secretion, is present on the β cell of the pancreas. A P_2X subtype, mediating vasoconstriction, is present on the vascular bed of the rat pancreas.