Phorbol ester has different effects on forskolin and beta-adrenergic-stimulated cAMP accumulation in mouse parotid acini.
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 (pPKC) 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 synthetic 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.
Watson
E L
EL
Department of Oral Biology, University of Washington, Seattle 98195.
Jacobson
K
K
Meier
K
K
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D010306:Parotid Gland / Q000187:drug effects* / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine