PHARMACOLOGICAL DISSOCIATION OF UTP-ELICITED AND ATP-ELICITED CONTRACTIONS AND RELAXATIONS IN ISOLATED RAT AORTA

Effects of UTP have been described in many tissues, but it is not clea r whether these are due to purinoceptors. Specific receptors for UTP, 'pyrimidinoceptors', and 'nucleotide receptors' have also been propose d. We pharmacologically characterized the receptors involved in the AT P- 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-m ethylene ATP > > ATP, and the desensitization by alpha,beta-methylene ATP suggests that ATP contractions were mediated via P-2X purinoceptor s 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 P-2Y purinoceptor. However, the relaxation se ems to be unrelated to the classical P-2Y 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 re laxation was produced via endothe lium-dependent and endothelium-indep endent mechanisms, unrelated to adenosine receptors. It is unlikely th at UTP-induced contractions and the endothelium-dependent relaxation w ere produced via purinoceptors since the pharmacology is not consisten t with that of the classical P-2 purinoceptors studied. Furthermore, U TP-sensitive receptors showed a pharmacological property that was also distinct from that of the 'nucleotide' or P-2U receptor reported. The results suggest the presence of a heterogeneous population of purinoc eptors and pyrimidinoceptors pharmacologically different from the rece ptors for ATP.