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 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 (pD₂ 6.6), a P_2Y receptor agonist.

7. Ca²⁺-mobilizing P_2U 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 μM suramin).

8. There was no evidence of a Ca²⁺-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 Ca²⁺ but is not coupled to vasomotor responses and (iii) a putative P_2Y receptor on vascular smooth muscle cells that induces relaxation via a Ca²⁺-independent signal transduction pathway.

Full Text

The Full Text of this article is available as a PDF (390.7 KB).