Characterization of the P2 receptors in rabbit pulmonary artery.

Abstract

1. We have identified the P2 receptors mediating vasomotor responses in the rabbit pulmonary artery. 2. Neither ATP nor UTP contracted intact or endothelium-denuded rings. However, both relaxed intact rings of rabbit pulmonary artery that had been preconstricted with phenylephrine (pD2 5.2 and 5.6, respectively). 3. The vasodilator effect of UTP was endothelium-dependent and abolished by the nitric oxide synthase inhibitor NG-nitro-L-arginine (L-NOARG). 4. The vasodilator effect of ATP was only partially inhibited by removal of endothelium or addition of L-NOARG, suggesting an additional direct effect on vascular smooth muscle. 5. The endothelium-dependent vasodilator responses to UTP and ATP were competitively antagonized by suramin. 6. Preconstricted, endothelium-denuded rings were also relaxed by 2-methylthio ATP (pD2 6.6), a P2Y receptor agonist. 7. Ca(2+)-mobilizing P2U receptors were identified on smooth muscle cells on the basis of single cell responses to ATP (pD2 7.8) and UTP (pD2 7.9; 6.7 in the presence of 100 microM suramin). 8. There was no evidence of a Ca(2+)-mobilizing P2Y receptor in these cultured cells. 9. The data suggest the presence of (i) a suramin-sensitive P2U receptor on endothelial cells that induces vasorelaxation through NO release, (ii) a suramin-sensitive P2U receptor on cultured smooth muscle cells that mobilizes Ca2+ but is not coupled to vasomotor responses and (iii) a putative P2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca(2+)-independent signal transduction pathway.