Evidence for two P2-purinoceptor subtypes in human small pulmonary arteries.

1. P2-purinoceptors have not been characterized in human pulmonary vessels and we therefore examined the effects of adenosine 5'-triphosphate (ATP) and its analogues on human isolated small pulmonary arteries (SPA) in vitro. 2. Contractile responses were induced by all of the analogues, with the rank order of potency alpha,beta-methylene-ATP (alpha,beta-meATP) = beta,gamma-methylene-ATP (beta,gamma-meATP) greater than ATP greater than 2-methylthio-ATP, indicating the presence of vasoconstrictor P2x receptors. 3. In precontracted SPA, vasodilator responses were produced by all of the analogues. The rank order of potency for the analogues causing vasodilator responses was: 2-methylthio-ATP much greater than ATP much greater than beta,gamma-meATP = alpha,beta-meATP, indicating a vasodilator P2y receptor. 4. Removal of endothelial cells had no significant effect on either the contractile or relaxant responses to any of the analogues. 5. After pretreatment of the endothelium-denuded vessels with alpha,beta-meATP (to desensitize P2x receptors), the contractile response to beta,gamma-meATP (a potent P2x receptor agonist) was abolished. 6. We conclude that both P2x- and P2y-purinoceptors are present in human SPA and that both receptors reside on the vascular smooth muscle.