P2Y purinoceptor and nucleotide receptor-induced relaxation of precontracted bovine aortic collateral artery rings: differential sensitivity to suramin and indomethacin.
We have examined a series of adenine nucleotides and UTP for their ability to cause relaxation of precontracted bovine aortic collateral artery rings. The overall rank order of agonist potency for relaxation was 2-methylthioadenosine 5'-triphosphate (2MeSATP) > adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) > UTP > ADP > ATP. These responses were endothelium-dependent. Interaction studies showed that responses to the selective P2Y purinoceptor agonist 2MeSATP, and to ADP, were mediated by different receptors from those mediating responses to UTP. Suramin, a P2 purinoceptor antagonist that binds to diverse sites for ATP, produced a concentration-dependent shift in the agonist concentration-effect curve to 2MeSATP, with a pKB of 5.45 +/- 0.15 and a slope of 0.94 +/- 0.09. Suramin produced a small, nonsignificant shift in the UTP response curve and had little effect on responses to ATP. Indomethacin (2.8 x 10(-6) M) had no effect on concentration-effect curves to UTP but almost abolished the relaxations produced by 2MeSATP and ADP. The concentration-effect curves to ATP and ATP gamma S showed a significant (P < .05) rightward shift in the presence of indomethacin. These results suggest the presence of separate P2Y purinoceptor and nucleotide receptors mediating endothelium-dependent relaxations of bovine aortic collateral artery smooth muscle. ATP acts at both receptors, whereas ADP acts at only one (P2Y). The effects of indomethacin show that these receptors differentially modulate the release of cyclooxygenase-derived mediators of relaxation.
Wilkinson
G F
GF
Department of Cell Physiology and Pharmacology, University of Leicester, United Kingdom.
McKechnie
K
K
Dainty
I A
IA
Boarder
M R
MR
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology*; D014544:Uridine Triphosphate / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D018048:Receptors, Purinergic P2; D009569:Nitric Oxide; D013498:Suramin; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate; D007213:Indomethacin