Dataset Information

Differential effects of uridine adenosine tetraphosphate on purinoceptors in the rat isolated perfused kidney.

ABSTRACT:

Background and purpose

Purinergic signalling plays an important role in vascular tone regulation in humans. We have identified uridine adenosine tetraphosphate (Up(4)A) as a novel and highly potent endothelial-derived contracting factor. Up(4)A induces strong vasoconstrictive effects in the renal vascular system mainly by P2X(1) receptor activation. However, other purinoceptors are also involved and were analysed here.

Experimental approach

The rat isolated perfused kidney was used to characterize vasoactive actions of Up(4)A.

Key results

After desensitization of the P2X(1) receptor by ?,?-methylene ATP (?,?-meATP), Up(4)A showed dose-dependent P2Y(2)-mediated vasoconstriction. Continuous perfusion with Up(4)A evoked a biphasic vasoconstrictor effect: there was a strong and rapidly desensitizing vasoconstriction, inhibited by P2X(1) receptor desensitization. In addition, there is a long-lasting P2Y(2)-mediated vasoconstriction. This vasoconstriction could be blocked by suramin, but not by PPADS or reactive blue 2. In preparations of the rat isolated perfused kidney model with an elevated vascular tone, bolus application of Up(4)A showed a dose-dependent vasoconstriction that was followed by a dose-dependent vasodilation. The vasoconstriction was in part sensitive to P2X(1) receptor desensitization by ?,?-meATP, and the remaining P2Y(2)-mediated vasoconstriction was only inhibited by suramin. The Up(4)A-induced vasodilation depended on activation of nitric oxide synthases, and was mediated by P2Y(1) and P2Y(2) receptor activation.

Conclusions and implications

Up(4)A activated P2X(1) and P2Y(2) receptors to act as a vasoconstrictor, whereas endothelium-dependent vasodilation was induced by P2Y(1/2) receptor activation. Up(4)A might be of relevance in the physiology and pathophysiology of vascular tone regulation.

SUBMITTER: Tolle M

PROVIDER: S-EPMC2990153 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Publications

Differential effects of uridine adenosine tetraphosphate on purinoceptors in the rat isolated perfused kidney.

Tölle Markus M Schuchardt Mirjam M Wiedon Annette A Huang Tao T Klöckel Lars L Jankowski Joachim J Jankowski Vera V Zidek Walter W van der Giet Markus M

British journal of pharmacology 20101001 3

<h4>Background and purpose</h4>Purinergic signalling plays an important role in vascular tone regulation in humans. We have identified uridine adenosine tetraphosphate (Up(4)A) as a novel and highly potent endothelial-derived contracting factor. Up(4)A induces strong vasoconstrictive effects in the renal vascular system mainly by P2X(1) receptor activation. However, other purinoceptors are also involved and were analysed here.<h4>Experimental approach</h4>The rat isolated perfused kidney was use ...[more]

PMID: 20880394

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Dataset Information

Differential effects of uridine adenosine tetraphosphate on purinoceptors in the rat isolated perfused kidney.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Differential effects of uridine adenosine tetraphosphate on purinoceptors in the rat isolated perfused kidney.

Similar Datasets

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