Characterization of the P₂ receptors in rabbit pulmonary artery

Abstract

1 We have identi®ed 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 e ect of UTP was endothelium-dependent and abolished by the nitric oxide synthaseThe vasodilator e ect of ATP was only partially inhibited by removal of endothelium or addition of L-NOARG, suggesting an additional direct e ect 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 identi®ed 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 mM 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.

Megazol combined with suramin: a chemotherapy regimen which reversed the CNS pathology in a model of human African trypanosomiasis in mice

“…Exchange systems were mediated by P-2 purinoceptors (Jeffrey et al 1994;Bhagwat & Williams 1997). Suramin is an antagonist ligand for P-2 purinoceptors located on endothelial cell and brain astrocyte membranes (King et al 1996;Centemeri et al 1997;Qasabian et al 1997), and could have altered this selective transport for the passage of some molecules including megazol. In the trypanosome, megazol is recognized by another P2 purine transporter (Carter et al cells in the parenchymal perivascular spaces (Figure 1a,c).…”

Purinergic Signaling and Blood Vessels in Health and Disease

“…In rabbit pulmonary arteries, relaxation to UTP was endothelium dependent, whereas relaxation to ATP was only partially inhibited by removing the endothelium (Qasabian et al, 1997). In contrast, ATP and 2-MeSATP evoked endothelium-dependent vasodilatation in the rat isolated pulmonary circulation, suggesting an involvement of P2Y 1 receptors; this involved NO but there was no evidence for a role of prostanoids (Hasséssian and Burnstock, 1995;Hakim et al, 1997).…”

Purinergic Signaling in the Airways

“…ATP and UTP, acting via endothelial P2Y 1 , P2Y 2 , and/or P2Y 4 receptors, elicits vasodilation of bovine and rabbit pulmonary arteries, partly via mobilization of intracellular Ca 2ϩ and subsequent prostacyclin release (Lustig et al, 1992;Chen et al, 1996;Qasabian et al, 1997). Shear stress evokes release of ATP from endothelial cells, which causes NO release and pulmonary vasodilation (Hasséssian et al, 1993;Kiefmann et al, 2009).…”