EFFECTS OF PHOSPHATE‐MODIFIED ADENINE NUCLEOTIDE ANALOGUES ON INSULIN SECRETION FROM PERFUSED RAT PANCREAS

Abstract

The effects of three methylene analogues of adenosine 5′‐triphosphate (ATP) or 5′‐diphosphate (ADP) have been studied on insulin secretion from the isolated perfused pancreas of the rat: 5′‐adenylmethylene diposphonate or β, γ‐methylene ATP, adenosine 5′‐α, β‐methylene triphosphate or α, β‐methylene ATP and adenosine 5′‐α, β‐methylene diphosphonate or α, β‐methylene ADP. β.γ‐Methylene ATP did not elicit any increase of insulin release; α, β‐methylene ATP and α, β‐methylene ADP induced a biphasic stimulation of insulin secretion; this effect was dose‐related between 1.65 and 165 μmol/1. Relative potency ATP/α, β‐methylene ATP was 1.2 and ATP/α, β‐methylene ADP was 0.31. Our results point to the importance of the steric and electronic characteristics of the polyphosphate chain of the analogues of ATP and ADP in inducing an insulin secretory effect. They support the hypothesis of a purine receptor for ATP and ADP. 1981 British Pharmacological Society