Evidence for a vasoconstriction-mediating receptor for UTP, distinct from the P2 purinoceptor, in rabbit ear artery

Summary

1. The mechanism of uridine 5′-triphosphate-(UTP-)induced vasoconstriction was studied in the rabbit ear artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure. 2. Noradrenaline, adenosine 5'-triphosphate (ATP) and UTP caused concentration-dependent vasoconstriction. ATP and UTP were approximately equipotent. 3. The vasoconstrictor effect of UTP 300 μmol/l was enhanced by a mixture of atropine, diphenhydramine and methysergide (1 μmol/l each) and not affected by indometacin 10 μmol/l. 4. Prazosin (0.01 –1 μmol/l) and phentolamine (1–10 μmol/l) reduced the vasoconstrictor effect of UTP 300 μmol/l by up to 34%. Prazosin 1 μmol/l failed to diminish the vasoconstrictor effect of UTP 300 μmol/l after the sympathetic nerves had been destroyed with 6-hydroxydopamine. 5. α, β-Methylene-ATP (10–50 μol/l) elicited transient vasoconstriction. Subsequently, vasoconstrictor responses to ATP 100 or 300 pmol/1 were reduced by 88%, whereas responses to UTP 100 gmol/1 were enhanced, responses to UTP 300 μmol/l decreased by only 32% and responses to UTP 1000 gmol/1 reduced by 74%. After in vitro-denervation with 6-hydroxydopamine or in the presence of phentolamine 1 μmol/l throughout, a, β-methylene-ATP (10–50 μmol/l) reduced the vasoconstrictor effect of UTP 300 μmol/l by 44% and 43%, respectively. 6. We suggest that, in the rabbit ear artery, the non-adrenergic and α, β-methylene-ATP-resistant vasoconstrictor response to UTP is mediated by a separate receptor mechanism, distinct from the P₂ purinoceptor.