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Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells

  • Allergy and Histamine
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Abstract

We have studied the effect of protein kinase C and protein kinase A activation, and phosphatase inhibition on two different stimuli with distinct mechanisms of action. The first stimulus is compound 48/80, and its action is mediated probably by a Gi-protein, while the other is sodium fluoride, which unspecifically activates G-proteins. We established a comparative study because the action of compound 48/80 is calcium-independent, while fluoride is strictly calcium-dependent. The activation of protein kinase C was attained with the phorbol esther 12-O-tetradecanoylphorbol-13-acetate, protein kinase A was activated by increasing cAMP levels with forskolin or rolipram, and the phosphatase activity was inhibited with okadaic acid (OA), which inhibits phosphatases type 1 and 2A. Our results show that OA enhances the response to fluoride and compound 48/80 in the absence of calcium, and we conclude that calcium has a negative feedback role on the cell response. Protein kinase A activation strongly inhibits the response to fluoride, and the results show a positive regulation of protein kinase C and a negative regulation of protein kinase A over fluoride response. As previously reported by other authors for the ionophore A23187, TPA notably potentiates the response to fluoride, which supports its possible modulatory role on extracellular calcium-dependent stimuli.

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Authors and Affiliations

  1. Departamentos de Farmacología y Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, E-27002, Lugo

    L. M. Botana, A. Alfonso, M. R. Vieytes, M. C. Louzao & A. G. Cabado

  2. Servicio de Endocrinologia, Hospital Valdecilla, Santander, Spain

    M. A. Botana

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  1. L. M. Botana
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  2. A. Alfonso
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  3. M. A. Botana
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  4. M. R. Vieytes
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  5. M. C. Louzao
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  6. A. G. Cabado
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Botana, L.M., Alfonso, A., Botana, M.A. et al. Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells. Agents and Actions 37, 1–7 (1992). https://doi.org/10.1007/BF01987883

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  • DOI: https://doi.org/10.1007/BF01987883

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