Characterization of the P 2 receptors in rabbit pulmonary artery

1 We have identified the P 2 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 (pD 2 5.2 and 5.6, respectively). 3 The vasodilator effect of UTP was endothelium‐dependent and abolished by the nitric oxide synthase inhibitor N G ‐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 (pD 2 6.6), a P 2Y receptor agonist. 7 Ca 2+ ‐mobilizing P 2U receptors were identified on smooth muscle cells on the basis of single cell responses to ATP (pD 2 7.8) and UTP (pD 2 7.9; 6.7 in the presence of 100 μm suramin). 8 There was no evidence of a Ca 2+ ‐mobilizing P 2Y receptor in these cultured cells. 9 The data suggest the presence of (i) a suramin‐sensitive P 2U receptor on endothelial cells that induces vasorelaxation through NO release, (ii) a suramin‐sensitive P 2U receptor on cultured smooth muscle cells that mobilizes Ca 2+ but is not coupled to vasomotor responses and (iii) a putative P 2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca 2+ ‐independent signal transduction pathway.