Evidence for two different P-2X-receptors mediating vasoconstriction of Ap(5)A and Ap(6)A in the isolated perfused rat kidney

1 The activation of various P-2-receptor subtypes in rat renal vasculature by P-1, P-5-diadenosine pentaphosphate (Ap(5)A) and P-1, P-6-diadenosine he xaphosphate (Ap(6)A) were studied by measuring their effects on perfusion p ressure during continuous perfusion in a rat isolated perfused kidney. 2 Permanent perfusion with Ap(5)A and Ap(6)A elicited both a transient and sustained vasoconstriction with both vasoconstrictions to be different: the transient vasoconstriction can be elicited with concentrations greater tha n or equal to 10 nM, whereas the sustained vasoconstriction is observed wit h concentrations greater than or equal to 1 nM. 3 Ap(5)A and Ap(6)A act via the same receptors as alpha,beta-methylene ATP (alpha,beta-meATP). 4 The rank order of potency for transient vasconstriction was alpha,beta-me ATP = Ap(5)A>Ap(6)A>beta,gamma-meATP, and for sustained vasoconstriction al pha,beta-meATP = Ap(5)A>beta,gamma-meATP greater than or equal to Ap(6)A. 5 Suramin, a non-selective P-2-receptor antagonist, and pyridoxal-phosphate -6-azophenyl-2;4-disulphonic acid (PPADS) a highly selective P-2x-receptor antagonist antagonized both the transient and the sustained vasoconstrictio n. 6 Taken together the results of the agonist profile of Ap(5)A and Ap(6)A an d comparing its findings to literature it can be demonstrated that the tran sient but not the sustained vasoconstriction is mediated via the P-2X1-rece ptor which is present in rat renal vasculature. 7 It is demonstrated that the agonist profile of the sustained vasoconstric tion induced by Ap(5)A and Ap(6)A does not fit to any currently known P2X- or P-2Y-receptor subtype. 8 We conclude a yet unidentified P-2X-receptor or chimeric P-2X-receptor ma y contribute to the effects on rat renal vasculature produced by Ap(5)A and Ap(6)A and which may play an important role in glomerular perfusion pressu re and blood pressure control.