Novel Blockade of Ca^<2+> Current by Quinacrine in Smooth Muscle Cells of the Guinea Pig
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概要
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Effects of quinacrine on voltage-dependent Ca<SUP>2+</SUP> channel current (I<SUB>Ca</SUB>) were examined using whole cell voltage clamp in single smooth muscle cells isolated from vas deferens and urinary bladder and single cardiac myocytes from ventricle of the guinea pig. When I<SUB>Ca</SUB> was elicited by depolarization from a holding potential of −60 to 0 mV for 150 msec every 15 sec in vas deferens myocytes, external application of quinacrine reduced the amplitude of I<SUB>Ca</SUB> in a concentration-dependent manner in a range of 0.1 ?? 30 μM, and the IC<SUB>50</SUB> of quinacrine was 1.3 μM. The block was at least partly removed by washout. The block of I<SUB>Ca</SUB> by 1 μM quinacrine in vas deferens myocytes greatly depended upon the activation potentials but only slightly on the holding potentials. Use-dependent development of the block was also observed. Addition of 300 μM quinacrine to the pipette-filling solution did not significantly affect I<SUB>Ca</SUB>. The IC<SUB>50</SUB> of quinacrine for I<SUB>Ca</SUB> block in urinary bladder myocytes was 1.1 μM and comparable to that in vas deferens. On the other hand, IC<SUB>50</SUB> for the block of I<SUB>Ca</SUB> elicited by depolarization from −45 to 0 mV in cardiac ventricular myocytes was 5.6 μM. It is concluded that quinacrine is a potent blocker of L-type Ca<SUP>2+</SUP> channels in two types of smooth muscle myocytes and that the potency appeared to be approximately five times higher than that in cardiac myocytes. The action of quinacrine may be due to the direct block of Ca<SUP>2+</SUP> channels from outside of the cell membrane.
- 社団法人 日本薬理学会の論文
著者
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Imaizumi Y
Dep. Of Molecular And Cellular Pharmacology Graduate School Of Pharmaceutical Sciences Nagoya City U
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Imaizumi Yuji
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Watanabe Minoru
Department Of Molecular And Cellular Pharmacology Nagoya City University
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NAGANO Norihiro
Department of Chemical Pharmacolgy, Faculty of Pharmaceutical Sciences, Nagoya City University
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Nagano Norihiro
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Ishii Yatsuka
Department Of Clinical Pharmacology And Therapeutics Oita Medical University
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Watanabe Minoru
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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Watanabe M
Department Of Molecular And Cellular Pharmacology Faculty Of Pharmaceutical Sciences Nagoya City Uni
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