EVIDENCE FOR 2 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

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 (ATPγS), and β,γ-imido adenosine 5′-triphosphate (AMP-PNP) elicited concentration-dependent vasoconstriction, whereas AMP, 2-methylthio-ATP, α, β-methylene-ATP and β,γ-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 ≫ UMP = CTP; that of the purine nucleotides was: ATPγS > AMP-PNP > ATP > ADP > 2-methylthio-ATP = α, β-methylene-ATP = β,γ-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; indometacin; nordihydroguaiaretic acid; denervation by 6-hydroxydopamine; or mechanical removal of endothelium. Prolonged exposure to α,β-methylene-ATP elicited only a very small vasoconstriction and did not change the constrictor effects of UTP or ATP. Prolonged exposure to ATPγS 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. ATP 10-3 mol/l elicited marked additional vasoconstriction after precontraction with UTP 10-3 mol/l, whereas UTP elicited only a very small additional vasoconstriction when its concentration was doubled from 10-3 to 2 × 10-3 mol/l. It is concluded that, in the rabbit basilar artery, the vasoconstrictor response to UTP is mediated by a pyrimidine nucleotide receptor which is distinct from the P2-purinoceptor, and that the vasoconstrictor response to ATP is mediated by a P2-receptor which is distinct from the known P2-subtypes. © 1990 Springer-Verlag.