Evidence for two different P2X-receptors mediating vasoconstriction of Ap5A and Ap6A in the isolated perfused rat kidney.
The activation of various P2-receptor subtypes in rat renal vasculature by P1, P5-diadenosine pentaphosphate (ApsA) and P1, P6-diadenosine hexaphosphate (Ap6A) were studied by measuring their effects on perfusion pressure during continuous perfusion in a rat isolated perfused kidney. Permanent perfusion with Ap5A and Ap6A elicited both a transient and sustained vasoconstriction with both vasoconstrictions to be different: the transient vasoconstriction can be elicited with concentrations > or = 10 nM, whereas the sustained vasoconstriction is observed with concentrations > or = 1 nM. ApsA and Ap6A act via the same receptors as alpha,beta-methylene ATP (alpha,beta-meATP). The rank order of potency for transient vasconstriction was alpha,beta-meATP = ApsA>Ap6A>B,gamma-meATP, and for sustained vasoconstriction alpha,beta-meATP = Ap5A > beta,gamma-meATP > or = Ap6A. Suramin, a non-selective P2-receptor antagonist, and pyridoxal-phosphate-6-azophenyl-2;4-disulphonic acid (PPADS) a highly selective P2X-receptor antagonist antagonized both the transient and the sustained vasoconstriction. Taken together the results of the agonist profile of Ap5A and Ap6A and comparing its findings to literature it can be demonstrated that the transient but not the sustained vasoconstriction is mediated via the P2X1-receptor which is present in rat renal vasculature. It is demonstrated that the agonist profile of the sustained vasoconstriction induced by ApsA and Ap6A does not fit to any currently known P2X- or P2Y-receptor subtype. We conclude a yet unidentified P2X-receptor or chimeric P2X-receptor may contribute to the effects on rat renal vasculature produced by Ap5A and Ap6A and which may play an important role in glomerular perfusion pressure and blood pressure control.
van der Giet
M
M
Ruhr-Universität Bochum, Marienhospital Herne, Med. Klinik I, Germany. Markus.vanderGiet@ruhr-uni-bochum.de
Cinkilic
O
O
Jankowski
J
J
Tepel
M
M
Zidek
W
W
Schlüter
H
H
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010477:Perfusion; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012077:Renal Artery / Q000187:drug effects / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D015226:Dinucleoside Phosphates; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D014662:Vasoconstrictor Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C070070:diadenosine 5',5''''-P1,P6-hexaphosphate; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate