A Carbamate-Type Cholinesterase Inhibitor 2-sec-Butylphenyl N-Methylcarbamate Insecticide Blocks L-Type Ca〔2+〕 Channnel in Guinea Pig Ventricular Myocytes

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  • Futagawa Haruko
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo Laboratory of Pharmacology, Department of Toxicology, The Institute of Environmental Toxicology
  • Takahashi Hiroaki
    Laboratory of Pharmacology, Department of Toxicology, The Institute of Environmental Toxicology
  • Nagao Taku
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo
  • Adachi-Akahane Satomi
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, University of Tokyo

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タイトル別名
  • A Carbamate-Type Cholinesterase Inhibitor 2-sec-Butylphenyl N-Methylcarbamate Insecticide Blocks L-Type Ca2+ Channel in Guinea Pig Ventricular Myocytes.
  • Carbamate Type Cholinesterase Inhibitor 2 sec Butylphenyl N Methylcarbamate Insecticide Blocks L Type Ca 2 Channnel in Guinea Pig Ventricular Myocytes

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説明

2-sec-Butylphenyl N-methylcarbamate (BPMC) is a carbamate-type cholinesterase (ChE) inhibitor with unique toxicological properties such as noncholinergic cardiovascular collapse. Effects of BPMC on L-type Ca2+ channel currents (ICa(L)) were studied in isolated guinea pig ventricular myocytes using the whole-cell patch-clamp technique, since the examination of cardiovascular responses indicated its Ca2+ antagonistic action. BPMC induced bradycardic and hypotensive responses in vivo and inhibited contraction of isolated papillary muscles (IC50 = 1.3 × 10− 4 M) in guinea pigs. BPMC produced reversible block of ICa(L) in the concentration range of 10 −4 – 10 −3 M. At test potentials between −30 mV and +20 mV, BPMC at 3 × 10 −4 M caused marked acceleration of decay rate of ICa(L) with moderate reduction of peak ICa(L) amplitude. BPMC (3 × 10 −4 M) shifted the steady-state inactivation curve to the hyperpolarizing direction by 12.7 mV. Decay rate of Ba2+ currents (IBa(L)) was also accelerated by BPMC. Fitting analysis of inactivation kinetics of IBa(L) with a two-exponential equation revealed that BPMC accelerates the slow inactivation component. At concentrations for blocking peak IBa(L) by ca. 30%, the inactivation kinetics of IBa(L) were significantly accelerated by BPMC, but merely slightly accelerated by Ca2+ channel antagonists such as diltiazem, nifedipine, or verapamil. These results indicate that BPMC, in addition to the inhibition of ChE, blocks L-type Ca2+ channels by accelerating voltage-dependent inactivation.

収録刊行物

  • Jpn.J.Pharmacol.

    Jpn.J.Pharmacol. 90 (1), 12-20, 2002

    公益社団法人 日本薬理学会

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