The regulation of aortic endothelial cells by purines and pyrimidines involves co-existing 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) (ADP beta S) were potent agonists (EC50 0.41 microM and 0.85 microM respectively) while beta, gamma-methylene ATP at 300 microM was not. 3. The cells also responded to UTP. The maximal response to UTP was less than that for either 2MeSATP and ADP beta S while adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S) gave the largest maximal response. 4. The concentration-effect curve to UTP was additive in the presence of either 2MeSATP or ADP beta S. However, the concentration-effect curves to ATP gamma S reached the same maximum in the presence or absence of UTP. 5. Suramin, at concentrations between 10 microM and 100 microM was a competitive antagonist for the response to ADP beta S 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.
Wilkinson
G F
GF
Department of Pharmacology and Therapeutics, University of Leicester.
Purkiss
J R
JR
Boarder
M R
MR
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D011685:Purine Nucleotides / Q000378:metabolism*; D011687:Purines / Q000378:metabolism*; D011743:Pyrimidines / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000378:metabolism*; D013498:Suramin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000378:metabolism
D007295:Inositol Phosphates; D011685:Purine Nucleotides; D011687:Purines; D011743:Pyrimidines; D011983:Receptors, Purinergic; D013498:Suramin; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D014544:Uridine Triphosphate