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Roles of Ca2+ and protein kinase C in regulation of prostaglandin E2 release by cultured rabbit gastric epithelial cells

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Abstract

Prostaglandin (PG) has been reported to be one of the important protective factors in the gastric mucosa. However the mechanism of the regulation of endogenous PG production has not been well studied. We investigated the possible roles of Ca2+, cAMP, and protein kinase C (PKC) in the regulation of PGE2 release from cultured rabbit gastric mucosal cells. PGE2 was measured by radioimmunoassay. A23187 (Ca2+ ionophore) at 2×10−6 M significantly increased PGE2 release. Deprivation of Ca2+ from the medium blocked the A23187-induced increase of PGE2. TMB-8 (a putative inhibitor of Ca2+ release from intracellular stores) did not have any significant effects on the increase of PGE2-induced by A23187. Thus, A23187 increased PGE2 through the influx of extracellular Ca2+. W7 or compound 48/80 (calmodulin inhibitors) did not alter the response of PGE2 caused by A23187. Exogenous administration of cAMP, forskolin (an activator of adenylate cyclase), or 2-chloroadenosine (a possible activator of adenylate cyclase through adenosine A2 receptor) had neither significant effects on PGE2 release nor an effect on A23187-induced increase of PGE2 release. 12-O-tetradecanoylphorbol 13-acetate (TPA, an activator of PKC) significantly stimulated PGE2 release in a dose-dependent fashion, whereas another phorbol ester with no biological activity did not. A23187 at 0.8×10−6 M, but not cAMP, potentiated the TPA-induced increase of PGE2. Mepacrine (a phospholipase A2 inhibitor) reduced the A23187-and TPA-induced increase of PGE2. These results suggest that Ca2+ and protein kinase C may play important roles in the regulation of PGE2 release by cultured rabbit gastric cells.

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  1. The Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, 113, Bunkyo-ku, Tokyo, Japan

    S. Ota MD, Y. Hata MD, A. Terano MD, K. Yoshiura MD, H. Hiraishi MD, T. Kawabe MD, H. Mutoh MD, S. Shiina MD & T. Sugimoto MD

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Ota, S., Hata, Y., Terano, A. et al. Roles of Ca2+ and protein kinase C in regulation of prostaglandin E2 release by cultured rabbit gastric epithelial cells. Digest Dis Sci 38, 1426–1434 (1993). https://doi.org/10.1007/BF01308599

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  • DOI: https://doi.org/10.1007/BF01308599

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