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Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein

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Abstract

In single rabbit aortic smooth muscle cells, and at a concentration known to induce a maximum sustained increase of intracellular Ca2+ via activation of the steady-state voltage dependent R-type Ca2+ channels, endothelin-1 (10-7 M) and insulin (80 μU/ml) were found to induce a sustained increase in cytosolic free Ca2+ ([Ca]i) levels that was significantly attenuated by pre-treatment with either pertussis toxin (PTX), cholera toxin (CTX) or removal of extracellular Ca2+.

However, both PTX and CTX failed to inhibit the sustained depolarization-evoked sustained Ca2+ influx and [Ca]i elevation via activation of the R-type Ca2+ channels. Moreover, ET-1 and insulin-evoked sustained increases in Ca2+ influx were not attenuated by the selective PKC inhibitor, bisindolylmaleimide (BIS), or the specific L-type Ca2+ channel blocker, nifedipine, but were completely reversed by the R-type Ca2+ channel blocker, (-) PN 200-110 (isradipine). These data suggest that both insulin and ET-1 activate the nifedipine-insensitive but isradipine-sensitive steady state voltage dependent R-type Ca2+ channels present on rabbit VSMCs and these channels are directly coupled to PTX and CTX sensitive G protein(s).

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Authors and Affiliations

  1. MRCC Group on Immuno-Cardiovascular Interaction, Department of Anatomy and Cell Biology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

    Radha Naik, Doris Jaalouk, Danielle Jacques, Demetri Economos, Pédro D'Orléans-Juste & Pierre Pothier

  2. Department of Pharmacology, Faculty of Medicine, Université de Sherbrooke, Sherbrooke, Québec, J1H 5N4, Canada

    Ghassan Bkaily

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  1. Ghassan Bkaily
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  7. Pierre Pothier
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Bkaily, G., Naik, R., Jaalouk, D. et al. Endothelin-1 and insulin activate the steady-state voltage dependent R-type Ca2+ channel in aortic smooth muscle cells via a pertussis toxin and cholera toxin sensitive G-protein. Mol Cell Biochem 183, 39–47 (1998). https://doi.org/10.1023/A:1006887714302

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