Evidence for two different P2X-receptors mediating vasoconstriction of Ap5A and Ap6A in the isolated perfused rat kidney
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Evidence for two different P2X-receptors mediating vasoconstriction of Ap5A and Ap6A in the isolated perfused rat kidney. / van der Giet, M; Cinkilic, O; Jankowski, J; Tepel, M; Zidek, W; Schlüter, H.
in: BRIT J PHARMACOL, Jahrgang 127, Nr. 6, 07.1999, S. 1463-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Evidence for two different P2X-receptors mediating vasoconstriction of Ap5A and Ap6A in the isolated perfused rat kidney
AU - van der Giet, M
AU - Cinkilic, O
AU - Jankowski, J
AU - Tepel, M
AU - Zidek, W
AU - Schlüter, H
PY - 1999/7
Y1 - 1999/7
N2 - 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.
AB - 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.
KW - Adenosine Triphosphate
KW - Animals
KW - Dinucleoside Phosphates
KW - Dose-Response Relationship, Drug
KW - In Vitro Techniques
KW - Kidney
KW - Male
KW - Perfusion
KW - Purinergic P2 Receptor Antagonists
KW - Pyridoxal Phosphate
KW - Rats
KW - Rats, Inbred WKY
KW - Receptors, Purinergic P2
KW - Renal Artery
KW - Renal Circulation
KW - Suramin
KW - Vasoconstriction
KW - Vasoconstrictor Agents
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/sj.bjp.0702667
DO - 10.1038/sj.bjp.0702667
M3 - SCORING: Journal article
C2 - 10455297
VL - 127
SP - 1463
EP - 1469
JO - BRIT J PHARMACOL
JF - BRIT J PHARMACOL
SN - 0007-1188
IS - 6
ER -
