Vasoconstrictor responses to the P2X‐purinoceptor agonist (β, γ‐methylene‐L‐ATP in human cutaneous and renal blood vessels
British Journal of Pharmacology(1995)
Abstract
Strips of human saphenous veins and of human renal arteries and veins were superfused with Krebs‐Henseleit solution at 37°C. Constrictor responses were elicited by exogenous noradrenaline and the P2X‐purinoceptor‐selective agonist, β,γ‐methylene‐L‐ATP In human saphenous veins, β,γ‐methylene‐L‐ATP (0.3–30 μm; EC50 2.2 μm) induced marked constrictor responses. The maximal response to β,γ‐methylene‐L‐ATP was similar to the maximal response to noradrenaline. The P2‐purinoceptor antagonist suramin (30 μm) shifted the concentration‐response curve of β,γ‐methylene‐L‐ATP to the right (apparent pKB value 4.8); suramin (100 μm) markedly inhibited the responses to P,y‐methylene‐L‐ATP. The preferential P2X‐purinoceptor antagonist, pyridoxal‐phosphate‐6‐azophenyl‐2,4,‐disulphonic acid (PPADS; 3 μm) slightly reduced the response to β,γ‐methylene‐L‐ATP. At a ten times higher concentration (30 μm), PPADS almost abolished the responses to p,y‐methylene‐L‐ATP. PPADS (30 μm), in contrast, caused no significant change in the concentration‐response curve of noradrenaline In extrarenal and intrarenal arteries, EC50 values and maximal responses to noradrenaline were similar when compared with responses to noradrenaline in saphenous veins. Noradrenaline also constricted extrarenal veins. However, in contrast to the results obtained on saphenous veins, p,y‐methylene‐L‐ATP caused almost no constrictor responses in extrarenal veins and arteries and only moderate responses in intrarenal arteries The results demonstrate marked differences in responsiveness of human blood vessels to the selective P2X‐purinoceptor agonist, β,γ‐methylene‐L‐ATP, suggesting tissue differences in the occurrence or operation of P2X‐purinoceptors in human vascular tissues. Moreover, the results indicate that PPADS blocks P2X‐purinoceptors in human isolated blood vessels as previously demonstrated in animal blood vessels.
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