Cicletanine-Induced Decreases in Cytosolic Ca^<2+> Level and Contraction in Vascular Smooth Muscle

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The mechanism by which cicletanine (3-(4-chlorophenyl)-1, 3-dihydro-7-hydroxy-6-methylfuro-[3, 4-<I>c</I>]pyridine) induces vasodilatation was examined in isolated vascular smooth muscle. Cicletanine inhibited the contraction induced by high K<SUP>+</SUP>, norepinephrine (NE) and prostaglandin F<SUB>2α</SUB> in a concentration-dependent manner in rat aorta. High K<SUP>+</SUP> (15.8 – 72.7 mM) elicited elevation of cytosolic Ca<SUP>2+</SUP> level ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) and contraction in a concentration-dependent manner. Cicletanine (300 μM) inhibited the high K<SUP>+</SUP>-induced contractions without changing the [Ca<SUP>2+</SUP>]<SUB>i</SUB>/tension relationship. NE (3 – 300 nM) elicited greater contractions than high K<SUP>+</SUP> at a given [Ca<SUP>2+</SUP>]<SUB>i</SUB>, suggesting that NE increased Ca<SUP>2+</SUP> sensitivity of the contractile elements. Cicletanine inhibited the NE-induced contractions without changing the slope of the [Ca<SUP>2+</SUP>]<SUB>i</SUB>/tension relationship. Cicletanine inhibited the transient increases in both [Ca<SUP>2+</SUP>]<SUB>i</SUB> and muscle tension elicited by NE but not the transient increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB> elicited by caffeine in Ca<SUP>2+</SUP>-free solution. Cicletanine did not inhibit contraction induced by Ca<SUP>2+</SUP> in the permeabilized rabbit mesenteric artery with α-toxin. These results suggest that cicletanine inhibits vascular smooth muscle contraction by multiple mechanisms: 1) inhibition of Ca<SUP>2+</SUP> influx via voltage-dependent Ca<SUP>2+</SUP> channel and 2) inhibition of Ca<SUP>2+</SUP> release mediated by the α-adrenoceptors, but not by caffeine.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 76(1), 57-63, 1998-01

    The Japanese Pharmacological Society

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各種コード

  • NII論文ID(NAID)
    10008191124
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4395858
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  NDL  J-STAGE 
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