Evidence for two P₂‐purinoceptor subtypes in human small pulmonary arteries

P 2 ‐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 . Contractile responses were induced by all of the analogues, with the rank order of potency α,β‐methylene‐ATP (α,β‐meATP) = β,γ‐methylene‐ATP (β,γ‐meATP) > ATP > 2‐methylthio‐ATP, indicating the presence of vasoconstrictor P 2x receptors. 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 ATP β,γ‐meATP = α,β‐meATP, indicating a vasodilator P 2y receptor. Removal of endothelial cells had no significant effect on either the contractile or relaxant responses to any of the analogues. After pretreatment of the endothelium‐denuded vessels with α,β‐meATP (to desensitize P 2x receptors), the contractile response to β,γ‐meATP (a potent P 2x receptor agonist) was abolished. We conclude that both P 2x ‐ and P 2y ‐purinoceptors are present in human SPA and that both receptors reside on the vascular smooth muscle.