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Molecular Pharmacology

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Research ArticleArticle

Effects of Almitrine Bismesylate on the Ionic Currents of Chemoreceptor Cells from the Carotid Body

J. R. López-López, M. T. Pérez-García, E. Canet and C. Gonzalez
Molecular Pharmacology February 1998, 53 (2) 330-339; DOI: https://doi.org/10.1124/mol.53.2.330
J. R. López-López
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M. T. Pérez-García
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E. Canet
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C. Gonzalez
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Abstract

Almitrine is a drug used in the treatment of hypoxemic chronic lung diseases such as bronchitis and emphysema because it is a potent stimulant of the carotid bodies in human and different animal species that produces a long-lasting enhancement of alveolar ventilation, ameliorating arterial blood gases. However, the mechanism of action of almitrine remains unknown. We investigated the effect of almitrine on ionic currents of chemoreceptor cells isolated from the carotid body of rat and rabbits by using the whole-cell and inside-out configurations of the patch-clamp technique. Almitrine at concentrations up to 10 μm did not affect whole-cell voltage-dependent K+, Ca2+, or Na+ currents in rat or rabbit cells. However, this concentration of almitrine significantly inhibited the Ca2+-dependent component of K+currents in rat chemoreceptor cells. This effect of almitrine on the Ca2+-dependent component of K+ currents was investigated further at the single-channel level in excised patches in the inside-out configuration. In this preparation, almitrine inhibited the activity of a high-conductance (152 ± 13 pS), Ca2+-dependent K+ channel by decreasing its open probability. The IC50 value of the effect was 0.22 μm. The inhibitory effect of almitrine on Ca2+-dependent K+ channels also was observed in GH3 cells. We conclude that almitrine inhibits selectively the Ca2+-dependent K+ channel and that in rat chemoreceptor cells, this inhibition could represent an important mechanism of action underlying the therapeutic actions of the drug.

Footnotes

    • Received September 22, 1997.
    • Accepted November 5, 1997.
  • Send reprint requests to: Prof. Constancio Gonzalez, Departmento de Bioquı́mica y Biologı́a Molecular y Fisiologı́a, Facultad de Medicina, Universidad de Valladolid, c/Ramón y Cajal 7, 47005 Valladolid, Spain. E-mail:constanciog{at}wamba.cpd.uva.es

  • This work was supported by Laboratories Servier (France) and Spanish Dirección General de Investigación Cientı́fica y Tecnológica Grant PB92/0267 (C.G.).

  • J.R.L.-L. and M.T.P.-G. contributed equally to this work.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 53 (2)
Molecular Pharmacology
Vol. 53, Issue 2
1 Feb 1998
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Research ArticleArticle

Effects of Almitrine Bismesylate on the Ionic Currents of Chemoreceptor Cells from the Carotid Body

J. R. López-López, M. T. Pérez-García, E. Canet and C. Gonzalez
Molecular Pharmacology February 1, 1998, 53 (2) 330-339; DOI: https://doi.org/10.1124/mol.53.2.330

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Research ArticleArticle

Effects of Almitrine Bismesylate on the Ionic Currents of Chemoreceptor Cells from the Carotid Body

J. R. López-López, M. T. Pérez-García, E. Canet and C. Gonzalez
Molecular Pharmacology February 1, 1998, 53 (2) 330-339; DOI: https://doi.org/10.1124/mol.53.2.330
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