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Title of Journal: Pflugers Arch Eur J Physiol

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Abbravation: Pflügers Archiv - European Journal of Physiology

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Springer Berlin Heidelberg

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DOI

10.1002/iroh.19680530108

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ISSN

1432-2013

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Enhanced uridine adenosine tetraphosphateinduced

Authors: Takayuki Matsumoto Shun Watanabe Ryusuke Kawamura Kumiko Taguchi Tsuneo Kobayashi
Publish Date: 2013/07/31
Volume: 466, Issue: 2, Pages: 331-342
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Abstract

The dinucleotide uridine adenosine tetraphosphate Up4A which has both purine and pyrimidine moieties was reported as a novel endotheliumderived contracting factor Recently growing evidence has suggested that Up4A plays an important role in regulation of the cardiovascular function We previously demonstrated that Up4Ainduced vasoconstrictions are altered in arteries from DOCAsalt hypertensive rats We have assessed responses to Up4A shown by renal arteries from type 2 diabetic GotoKakizaki GK rats 42–46 weeks old and identified the molecular mechanisms involved Concentrationdependent contractions to Up4A were greater in renal arterial rings from the GK than agematched control Wistar group In both groups the inhibition of nitric oxide synthase with N Gnitrolarginine increased the response to Up4A whereas the inhibition of cyclooxygenase COX with indomethacin decreased the response Specific inhibitors of COX1 valeroyl salicylate and COX2 NS398 a thromboxane TX receptor TP antagonist SQ29548 and P2 receptor antagonist suramin also decreased the response to Up4A Protein expressions of COXs in renal arteries were greater in the GK than Wistar group The production of TXB2 a metabolite of TXA2 by Up4A did not differ between these groups Concentrationdependent contractions to U46619 an agonist of the TP receptor were greater in renal arteries from the GK than Wistar group The expression of P2X1 and P2Y2 receptors did not differ between these groups These results suggest that enhancement of the Up4Ainduced contraction in renal arteries from GK rats may be attributable to the increased activation of COXs/TP receptor signalingWe thank S Natori M Mori M Fujii Y Matsuba C Kanazu and M Toba for technical help This study was supported in part by the Ministry of Education Culture Sports Science and Technology Japan and by the Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan

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