THE REGULATION OF AORTIC ENDOTHELIAL-CELLS BY PURINES AND PYRIMIDINES INVOLVES COEXISTING P2Y-PURINOCEPTORS AND NUCLEOTIDE RECEPTORS LINKED TO PHOSPHOLIPASE-C

1 We have examined the phospholipase C responses in bovine aortic endothelial cells to purines (ATP, ADP and analogues) and the pyrimidine, uridine triphosphate (UTP). 2 The cells responded to purines in a manner consistent with the presence of P2y purinoceptors; both 2-methylthioadenosine 5'-triphosphate (2MeSATP) and adenosine 5'-0-(2-thiodiphosphate) (ADPbetaS) were potent agonists (EC50 0.41 mum and 0.85 mum respectively) while beta, gamma-methylene ATP at 300 mum was not. 3 The cells also responded to UTP. The maximal response to UTP was less than that for either 2MeSATP and ADPbetaS while adenosine 5'-0-(3-thiotriphosphate) (ATPgammaS) gave the largest maximal response. 4 The concentration-effect curve to UTP was additive in the presence of either 2MeSATP or ADPbetaS. However, the concentration-effect curves to ATPgammaS reached the same maximum in the presence or absence of UTP. 5 Suramin, at concentrations between 10 mum and 100 mum was a competitive antagonist for the response to ADPbetaS and 2MeSATP but not the response to UTP. 6 The results show that there are two separate, co-existing, receptor populations: P2y-purinoceptors (responding to purines) and nucleotide receptors (responding to both purines and pyrimidines). We conclude that purines such as ATP/ADP may regulate aortic endothelial cells by interacting with two phospholipase C-linked receptors.