Mechanism of Membrane Depolarization Involved in α<sub>1A</sub>-Adrenoceptor-Mediated Contraction in Rat Tail and Iliac Arteries

  • Ishida Hirotake
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • Saito Shin-ya
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • Dohi Naoki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka
  • Ishikawa Tomohisa
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka

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  • Mechanism of Membrane Depolarization Involved in α[1A]-Adrenoceptor-Mediated Contraction in Rat Tail and Iliac Arteries

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Abstract

<p>Our previous studies have shown that phenylephrine-induced contraction of cutaneous arteries is primarily mediated via α1A-adrenoceptors, but not α1D-adrenoceptors that generally mediate vascular contraction, and that the larger part of the contraction is induced in a voltage-dependent Ca2+ channel (VDCC)-independent manner. Here, we investigated the mechanism underlying the smaller part of the α1A-adrenoceptor-mediated contraction, i.e., VDCC-dependent one, in cutaneous arteries. Isometric contraction was measured with wire myograph in endothelium-denuded tail and iliac arterial rings isolated from male Wistar rats. LOE908 (10 µM), a cation channel blocker, partially inhibited the contraction induced by phenylephrine in tail and iliac arteries. Nifedipine (10 µM) further suppressed the phenylephrine-induced contraction that remained in the presence of LOE908 (10 µM) in iliac arteries but barely in tail arteries, suggesting that phenylephrine-induced depolarization in tail arteries is due to the activation of LOE908-sensitive cation channels. In iliac arteries, the contraction induced by A-61603, a specific α1A-adrenoceptor agonist, was also partially inhibited by LOE908 (10 µM); however, nifedipine had little effect on the A-61603-induced contraction that remained in the presence of LOE908 (10 µM), suggesting that depolarization mediated via α1A-adrenoceptors is due to the activation of LOE908-sensitive cation channels even in iliac arteries. These results suggest that membrane depolarization mediated via α-adrenoceptors is caused by cation influx through LOE908-sensitive cation channels. Less contribution of VDCC to phenylephrine-induced contraction in tail arteries compared to in iliac arteries is likely due to that α-adrenoceptor-mediated activation of VDCC is caused only by depolarization via cation influx through LOE908-sensitive cation channels.</p>

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