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Phorbol esters induce a slow, non-cytotoxic release of histamine from rat peritoneal mast cells

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Abstract

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG) were employed to investigate the consequences of protein kinase C activation in rat peritoneal mast cells. TPA (10 ng/ml) induced a biphasic release of histamine from mast cells. At short periods of incubation histamine release was low; about 10% at 10 min. At 15 min a second phase of release commenced, achieving a maximum at 90 min incubation by which time about 70% of cell histamine was released. Histamine release by TPA was dependent on glycolytic and oxidative metabolism, temperature-dependent and occurred in purified mast cells. In contrast, histamine release induced by OAG 50 μg/ml was maximal after 20 min. Studies usign RHC 80267, a diacylglycerol (DAG) lipase inhibitor, indicated that metabolism of OAG by DAG lipase as well as spontaneous degradation accounts for the comparatively short-lived response to OAG.

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Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK

    M. E. Cantwell & J. C. Foreman

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  1. M. E. Cantwell
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  2. J. C. Foreman
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Cantwell, M.E., Foreman, J.C. Phorbol esters induce a slow, non-cytotoxic release of histamine from rat peritoneal mast cells. Agents and Actions 20, 165–168 (1987). https://doi.org/10.1007/BF02074658

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