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Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis

  • Molecular and cellular mechanisms of disease
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Abstract

The dinucleotide uridine adenosine tetraphosphate (Up4A), which has both purine and pyrimidine moieties, was reported as a novel endothelium-derived contracting factor. Recently, growing evidence has suggested that Up4A plays an important role in regulation of the cardiovascular function. We previously demonstrated that Up4A-induced vasoconstrictions are altered in arteries from DOCA-salt hypertensive rats. We have assessed responses to Up4A shown by renal arteries from type 2 diabetic Goto-Kakizaki (GK) rats (42–46 weeks old) and identified the molecular mechanisms involved. Concentration-dependent contractions to Up4A were greater in renal arterial rings from the GK than age-matched control Wistar group. In both groups, the inhibition of nitric oxide synthase (with N G-nitro-l-arginine) increased the response to Up4A, whereas the inhibition of cyclooxygenase (COX) (with indomethacin) decreased the response. Specific inhibitors of COX-1 (valeroyl salicylate) and COX-2 (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. Concentration-dependent 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 Up4A-induced contraction in renal arteries from GK rats may be attributable to the increased activation of COXs/TP receptor signaling.

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Acknowledgments

We 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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  1. Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo, 142-8501, Japan

    Takayuki Matsumoto, Shun Watanabe, Ryusuke Kawamura, Kumiko Taguchi & Tsuneo Kobayashi

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  1. Takayuki Matsumoto
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  2. Shun Watanabe
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Correspondence to Tsuneo Kobayashi.

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Matsumoto, T., Watanabe, S., Kawamura, R. et al. Enhanced uridine adenosine tetraphosphate-induced contraction in renal artery from type 2 diabetic Goto-Kakizaki rats due to activated cyclooxygenase/thromboxane receptor axis. Pflugers Arch - Eur J Physiol 466, 331–342 (2014). https://doi.org/10.1007/s00424-013-1330-0

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