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Research ArticleArticle

Carbamazepine-Induced Up-regulation of Voltage-dependent Na+ Channels in Bovine Adrenal Medullary Cells in Culture

Reiji Yoshimura, Nobuyuki Yanagihara, Takeshi Terao, Yasuhito Uezono, Yumiko Toyohira, Susumu Ueno, Kazuhiko Abe and Futoshi Izumi
Journal of Pharmacology and Experimental Therapeutics November 1998, 287 (2) 441-447;
Reiji Yoshimura
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Nobuyuki Yanagihara
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Takeshi Terao
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Yasuhito Uezono
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Yumiko Toyohira
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Susumu Ueno
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Kazuhiko Abe
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Futoshi Izumi
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Abstract

Treatment of cultured bovine adrenal medullary cells with carbamazepine (CBZ) for 5 days caused an increase in catecholamine secretion induced by veratridine, an activator of voltage-dependent Na+channels. However, no increase was stimulated by carbachol, an agonist of nicotinic receptors, or by 56 mM K+, a depolarizing agent that activates voltage-dependent Ca++ channels. CBZ (30 μg/ml) treatment enhanced veratridine-induced catecholamine secretion in a time-dependent manner (increases of 25%, 65% and 70% for 3, 5 and 7 days of treatment, respectively). CBZ treatment (5 days) increased veratridine-induced catecholamine secretion in a concentration-dependent manner (increases of 27%, 36%, 45% and 55% at 10, 15, 20 and 30 μg/ml of CBZ, respectively). CBZ treatment also increased 22Na+ influx and45Ca++ influx stimulated by veratridine. The stimulatory effect of CBZ treatment on catecholamine secretion was blocked by either actinomycin D or cycloheximide, an inhibitor of protein synthesis. Additive responses of catecholamine secretion and22Na+ influx induced by veratridine were associated with combined exposure of the cells to CBZ and dibutyryl cyclic AMP. CBZ treatment (30 μg/ml, 5 days) significantly increased the specific binding of [3H]saxitoxin to cell membranes. A Scatchard analysis of [3H]saxitoxin binding revealed that CBZ increased the Bmax value without any change in the dissociation constant. These findings suggest that CBZ up-regulates the density and activity of voltage-dependent Na+ channels.

Footnotes

  • Send reprint requests to: Dr. Nobuyuki Yanagihara, Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.

  • Abbreviations:
    CBZ
    carbamazepine
    dbc AMP
    dibutyryl cyclic AMP
    H89
    N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide
    KRP
    Krebs-Ringer phosphate
    STX
    saxitoxin
    TTX
    tetrodotoxin
    Kd
    dissociation constant
    GABA
    γ-aminobutyric acid
    NMDA
    N-methyl-d-aspartate
    Eagle’s MEM
    Eagle’s minimum essential medium
    DMSO
    dimethyl sulfoxide
    • Received September 30, 1997.
    • Accepted April 30, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 287, Issue 2
1 Nov 1998
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Research ArticleArticle

Carbamazepine-Induced Up-regulation of Voltage-dependent Na+ Channels in Bovine Adrenal Medullary Cells in Culture

Reiji Yoshimura, Nobuyuki Yanagihara, Takeshi Terao, Yasuhito Uezono, Yumiko Toyohira, Susumu Ueno, Kazuhiko Abe and Futoshi Izumi
Journal of Pharmacology and Experimental Therapeutics November 1, 1998, 287 (2) 441-447;

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Research ArticleArticle

Carbamazepine-Induced Up-regulation of Voltage-dependent Na+ Channels in Bovine Adrenal Medullary Cells in Culture

Reiji Yoshimura, Nobuyuki Yanagihara, Takeshi Terao, Yasuhito Uezono, Yumiko Toyohira, Susumu Ueno, Kazuhiko Abe and Futoshi Izumi
Journal of Pharmacology and Experimental Therapeutics November 1, 1998, 287 (2) 441-447;
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