Phorbol ester has different effects on forskolin and β-adrenergic-stimulated cAMP accumulation in mouse parotid acini

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Abstract

Phorbol 12-myristate 13-acetate (TPA) augmented the effects of forskolin, and inhibited the effects of isoproterenol on cAMP accumulation in mouse parotid acini. Treatment of intact cells with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (MIX), blocked TPA inhibition of isoproterenol but not forskolin-stimulated cAMP accumulation. TPA also caused the translocation of protein kinase C (PKC) from cytosol to membrane. Pre-treatment of parotid acini with TPA for 30 min enhanced the forskolin and isoproterenol-stimulated adenylate cyclase activity in isolated parotid membranes. Addition of purified PKC (nPKC) to parotid membranes mimicked the effects of TPA in increasing cAMP synthesis; the effects were blocked in the absence of calcium and phospholipid, and in the presence of the systhetic peptide (PKC 19-36). Purified PKC also mimicked the effects of TPA in augmenting forskolin and isoproterenol-stimulated adenylate cyclase activities in the cell-free system. Data suggest that the differential regulation of forskolin and isoproterenol-stimulated cAMP accumulation by TPA results from modification of enzymes that synthesize and degrade cAMP. © 1993.

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Watson, E. L., Jacobson, K., & Meier, K. (1993). Phorbol ester has different effects on forskolin and β-adrenergic-stimulated cAMP accumulation in mouse parotid acini. Cellular Signalling, 5(5), 583–592. https://doi.org/10.1016/0898-6568(93)90053-O

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