Evidence for two separate vasoconstriction-mediating nucleotide receptors, both distinct from the P2X-receptor, in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides

Abstract

Uridine 5'-triphosphate- (UTP-) and adenosine 5'-triphosphate- (ATP) induced vasoconstriction was studied in the rabbit basilar artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure. Serotonin, histamine and noradrenaline caused concentration-dependent vasoconstriction, with potency decreasing in that order. Of the nucleotides tested, UTP, UDP, UMP, CTP, ATP, ADP, adenosine 5'-O-(3-thio)-triphosphate (ATP gamma S), and beta,gamma-imido adenosine 5'-triphosphate (AMP-PNP) elicited concentration-dependent vasoconstriction, whereas AMP, 2-methylthio-ATP, alpha,beta-methylene-ATP and beta,gamma-methylene-ATP up to 10(-3) mol/l caused no or only a very small increase in perfusion pressure. The order of potency of the pyrimidine nucleotides was: UTP = UDP much greater than UMP = CTP; that of the purine nucleotides was: ATP gamma S greater than AMP-PNP greater than ATP greater than ADP greater than 2-methylthio-ATP = alpha,beta-methylene-ATP = beta,gamma-methylene-ATP. The vasoconstrictor effects of UTP and ATP were not or only to a minor degree influenced by: phentolamine; a mixture of atropine, diphenhydramine and methysergide; indomethacin; nordihydroguaiaretic acid; denervation by 6-hydroxydopamine; or mechanical removal of endothelium. Prolonged exposure to alpha,beta-methylene-ATP elicited only a very small vasoconstriction and did not change the constrictor effects of UTP or ATP. Prolonged exposure to ATP gamma S elicited marked vasoconstriction; subsequently, responses to ATP were reduced whereas those to UTP were, if anything, slightly enhanced. Reactive blue 2 reduced neither the UTP- nor the ATP-induced vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)