1982•British Journal of PharmacologyOpen access

ADENOSINE 5′‐DIPHOSPHATE ANTAGONISTS AND HUMAN PLATELETS: NO EVIDENCE THAT AGGREGATION AND INHIBITION OF STIMULATED ADENYLATE CYCLASE ARE MEDIATED BY DIFFERENT RECEPTORS

Noel J. Cusack, S.M.O. Hourani

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Abstract

1 Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; it has been suggested that these two effects are mediated by separate ADP receptors on the platelet surface. 2 Adenosine 5'-triphosphate and seven adenine nucleotide analogues were tested as inhibitors of both effects of ADP on human platelets, and were found to be competitive. 3 pA2 values were calculated for each antagonist for inhibition of both effects of ADP, and a good correlation (correlation coefficient 0.87; p less than 0.01) was found between the pA2 values for inhibition of ADP-induced aggregation and the pA2 values for inhibition of the effect of ADP on stimulated adenylate cyclase. 4 Such a correlation does not support the suggestion that ADP-induced aggregation and the inhibition by ADP of stimulated adenylate cyclase are mediated by two separate receptors.

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1 Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; it has been suggested that these two effects are mediated by separate ADP receptors on the platelet surface. 2 Adenosine 5'-triphosphate and seven adenine nucleotide analogues were tested as inhibitors of both effects of ADP on human platelets, and were found to be competitive. 3 pA2 values were calculated for each antagonist for inhibition of both effects of ADP, and a good correlation (correlation coefficient 0.87; p less than 0.01) was found between the pA2 values for inhibition of ADP-induced aggregation and the pA2 values for inhibition of the effect of ADP on stimulated adenylate cyclase. 4 Such a correlation does not support the suggestion that ADP-induced aggregation and the inhibition by ADP of stimulated adenylate cyclase are mediated by two separate receptors.

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1 Adenosine 5'-diphosphate (ADP) induces human platelet aggregation and noncompetitively inhibits stimulated human platelet adenylate cyclase; it has been suggested that these two effects are mediated by separate ADP receptors on the platelet surface. 2 Adenosine 5'-triphosphate and seven adenine nucleotide analogues were tested as inhibitors of both effects of ADP on human platelets, and were found to be competitive. 3 pA2 values were calculated for each antagonist for inhibition of both effects of ADP, and a good correlation (correlation coefficient 0.87; p less than 0.01) was found between the pA2 values for inhibition of ADP-induced aggregation and the pA2 values for inhibition of the effect of ADP on stimulated adenylate cyclase. 4 Such a correlation does not support the suggestion that ADP-induced aggregation and the inhibition by ADP of stimulated adenylate cyclase are mediated by two separate receptors.

Key concepts: Adenylate kinase, Cyclase, Adenosine diphosphate, Adenosine, Receptor, Adenine nucleotide, Platelet, Chemistry

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ADENOSINE 5′‐DIPHOSPHATE ANTAGONISTS AND HUMAN PLATELETS: NO EVIDENCE THAT AGGREGATION AND INHIBITION OF STIMULATED ADENYLATE CYCLASE ARE MEDIATED BY DIFFERENT RECEPTORS — Research Paper | ScholarLens