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Research ArticleArticle

Purification of a New Dimeric Protein from Cliona vastifica Sponge, which Specifically Blocks a Non-L-Type Calcium Channel in Mouse Duodenal Myocytes

Jean-Luc Morel, Hervé Drobecq, Pierre Sautiere, André Tartar, Jean Mironneau, Janti Qar, Jean-Louis Lavie and Michel Hugues
Molecular Pharmacology June 1997, 51 (6) 1042-1052; DOI: https://doi.org/10.1124/mol.51.6.1042
Jean-Luc Morel
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Hervé Drobecq
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Pierre Sautiere
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André Tartar
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Jean Mironneau
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Janti Qar
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Jean-Louis Lavie
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Michel Hugues
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Abstract

Marine sponges are synthesizing a wide variety of peptidic and organic molecules with biological activities. Multiple-step purification ofCliona vastifica extract led to a new dimeric peptide (mapacalcine; M r = 19,064) that is composed of two homologous chains, each containing nine cysteins. This protein has been found to selectively block a new calcium conductance characterized in mouse duodenal myocytes with an IC50 value of ∼0.2 μm. The mapacalcine-sensitive current was a non-L-type calcium current activated from a holding potential of −80 mV that persisted during stimulation of the cell at high frequencies (0.1–0.2 Hz) within 5–10 min. Time constants of inactivation were similar for both L-type and non-L-type calcium currents. The non-L-type calcium current of duodenal myocytes was not blocked by the pharmacological agents specific for N-, L-, P-, or Q-type calcium channels. Mapacalcine was unable to block T-type calcium current in portal vein myocytes as well as voltage-dependent potassium currents and calcium-activated chloride currents in duodenal and portal vein cells. Mapacalcine did not affect caffeine-induced calcium responses, indicating that it did not interfere with intracellular calcium stores. Competition experiments on mouse intestinal membranes showed that mapacalcine did not interact with dihydropyridines receptors. These data suggest that mapacalcine may be a specific inhibitor of a new type of calcium current, first identified in duodenal myocytes.

Footnotes

    • Received December 20, 1996.
    • Accepted March 10, 1997.
  • Send reprint requests to: Dr. Michel Hugues, CNRS ESA 5017, Physiopathologie et Pharmacologie Vasculaire, Université de Bordeaux II, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France. E-mail:michel.hugues{at}hippocrate.u-bordeaux2.fr

  • This work was supported by grants from the Fondation pour la Recherche Médicale, Pôle Médicament Aquitaine, and Région Aquitaine France.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 51 (6)
Molecular Pharmacology
Vol. 51, Issue 6
1 Jun 1997
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Research ArticleArticle

Purification of a New Dimeric Protein from Cliona vastifica Sponge, which Specifically Blocks a Non-L-Type Calcium Channel in Mouse Duodenal Myocytes

Jean-Luc Morel, Hervé Drobecq, Pierre Sautiere, André Tartar, Jean Mironneau, Janti Qar, Jean-Louis Lavie and Michel Hugues
Molecular Pharmacology June 1, 1997, 51 (6) 1042-1052; DOI: https://doi.org/10.1124/mol.51.6.1042

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Research ArticleArticle

Purification of a New Dimeric Protein from Cliona vastifica Sponge, which Specifically Blocks a Non-L-Type Calcium Channel in Mouse Duodenal Myocytes

Jean-Luc Morel, Hervé Drobecq, Pierre Sautiere, André Tartar, Jean Mironneau, Janti Qar, Jean-Louis Lavie and Michel Hugues
Molecular Pharmacology June 1, 1997, 51 (6) 1042-1052; DOI: https://doi.org/10.1124/mol.51.6.1042
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