Constriction of the smooth muscle of rat tail and femoral arteries and dog saphenous vein is induced by uridine triphosphate via 'pyrimidinoceptors', and by adenosine triphosphate via P2x purinoceptors.
Adenosine triphosphate (ATP) and uridine triphosphate (UTP) receptors were studied by comparing the contractile responses to UTP with those to ATP in the rat tail and femoral arteries and dog saphenous vein, after endothelium removal confirmed by histology, and near abolition of relaxation to acetylcholine. Contractions induced by ATP and UTP were dose dependent, as assessed from preparations at resting tension. Contraction curves were very different: rapid subsidence with ATP and sustained contraction with UTP. In the rat tail artery and the dog saphenous vein, quinidine, nordihydroguaiaretic acid (NDGA) and phentolamine inhibited the contractions induced by ATP, whereas those induced by UTP were only slightly reduced in the presence of NDGA and were not antagonized by quinidine and phentolamine. In all three vessels, alpha-beta methylene ATP induced desensitization to ATP, whereas it did not antagonize the UTP-induced contractions. Reactive blue 2 was incapable of antagonizing contractions to ATP and UTP in these preparations. In addition, UTP-induced contractions were hardly inhibited in a calcium-free Krebs solution, whereas ATP was totally inhibited. We showed that a calcium antagonist, nicardipine, was more potent on the UTP-induced than on the ATP-induced contractions. These results showed the UTP-induced contraction to be mediated by a new class of receptors, qualified here as 'pyrimidinoceptors', for which no antagonist is known. These results were obtained in the tail and femoral arteries of the rat and from the dog saphenous vein. ATP induced contraction in these three vessels via P2x purinoceptors. P2x purinoceptors and 'pyrimidinoceptors' are localized on the vascular smooth muscle.
Saïag
B
B
Laboratoire de Physiologie, UFR de Pharmacie, Rennes, France.
Milon
D
D
Allaín
H
H
Rault
B
B
Van den Driessche
J
J
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D005263:Femoral Artery; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D012501:Saphenous Vein; D013623:Tail / Q000098:blood supply; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011743:Pyrimidines; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate