Pharmacological dissociation of UTP- and ATP-elicited contractions and relaxations in isolated rat aorta.
Effects of UTP have been described in many tissues, but it is not clear whether these are due to purinoceptors. Specific receptors for UTP, 'pyrimidinoceptors', and 'nucleotide receptors' have also been proposed. We pharmacologically characterized the receptors involved in the ATP- and UTP-induced contraction under basal tone and the relaxation of raised tone elicited by noradrenaline in isolated rat aorta. The rank order of potency for the agonists for the contraction was alpha,beta-methylene ATP > > ATP, and the desensitization by alpha,beta-methylene ATP suggests that ATP contractions were mediated via P2X purinoceptors which were located on the vascular smooth muscle. The rank order of potency of the agonists for relaxation was 2-methyl-thio ATP > > ATP, which is suggestive of a P2Y purinoceptor. However, the relaxation seems to be unrelated to the classical P2Y subtype and a heterogeneous population of purinoceptors might therefore exist. The evidence comes from the distinct location and the different pharmacological effect of reactive blue 2 on 2-methyl-thio ATP and ATP receptors. 2-Methyl-thio ATP produced an endothelium-dependent relaxation while ATP-induced relaxation was produced via endothelium-dependent and endothelium-independent mechanisms, unrelated to adenosine receptors. It is unlikely that UTP-induced contractions and the endothelium-dependent relaxation were produced via purinoceptors since the pharmacology is not consistent with that of the classical P2 purinoceptors studied. Furthermore, UTP-sensitive receptors showed a pharmacological property that was also distinct from that of the 'nucleotide' or P2U receptor reported. The results suggest the presence of a heterogeneous population of purinoceptors and pyrimidinoceptors pharmacologically different from the receptors for ATP.
Garcia-Velasco
G
G
Laboratorio de Farmacologia, Departamento de Medicina, Facultad de Medicina, Oviedo, Spain.
Sanchez
M
M
Hidalgo
A
A
Garcia de Boto
M J
MJ
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D011956:Receptors, Cell Surface; D018048:Receptors, Purinergic P2; C074644:uridine triphosphate receptors; D000255:Adenosine Triphosphate; D014544:Uridine Triphosphate