Actions mediated by P2-purinoceptor subtypes in the isolated perfused mesenteric bed of the rat

1. The effects of adenosine 5'-triphosphate (ATP) and its analogues on the perfusion pressure of the isolated mesenteric bed of the rat were examined in preparations at resting tone, and with tone raised by noradrenaline. 2. In the preparations at resting tone, the effect of the analogues was to produce vasoconstriction, their rank order of potency being alpha,beta-methylene ATP greater than 2-methylthio ATP greater than ATP. 3. In raised tone preparations, dose-dependent vasodilatations were produced by ATP and 2-methylthio ATP although, at the highest doses tested, responses decreased in magnitude. The rank order of potency of the analogues in eliciting this vasodilator response was 2-methylthio ATP greater than ATP, while alpha,beta-methylene ATP was without effect. 4. Following desensitization of contractile responses to alpha,beta-methylene ATP, contractile responses to ATP and 2-methylthio ATP were abolished while their relaxant responses were potentiated. 5. Removal of the endothelium with sodium deoxycholate totally abolished the vasodilator responses and enhanced the contractile responses. 6. It is concluded that, in the rat mesentery, ATP and its analogues cause vasoconstriction via P2x-purinoceptors and vasodilatation via P2y-purinoceptors and that these are located on the smooth muscle and on the endothelium, respectively.