Phorbol ester modulation of cyclic AMP accumulation in a primary culture of rat aortic smooth muscle cells.
Over the past few years, the importance of calcium and cyclic AMP in the regulation of vascular smooth muscle tone has been well documented. We used a primary culture of rat aortic myocytes to study the effect of protein kinase C on isoproterenol- and forskolin-stimulated cyclic AMP production. Addition of the protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA) to these cells, but not an inactive analog, increased the stimulation of cyclic AMP production induced with isoproterenol or forskolin without changes in the apparent affinity of these compounds but did not affect the basal cAMP level. TPA also enhanced the cholera toxin-stimulated cyclic AMP accumulation. Isoproterenol and cholera toxin increased the forskolin apparent potency suggesting that interaction of activatory GTP-dependent protein with the catalytic subunit of adenylate cyclase facilitates forskolin interaction to the catalytic subunit. Treatment of myocytes with pertussis toxin had no effect on the basal level of cyclic AMP production and did not significantly modify isoproterenol- and forskolin-induced stimulation. Pertussis toxin treatment of cells did not affect the TPA-enhanced isoproterenol or forskolin stimulations suggesting that pertussis toxin and TPA actions would not share a common target of myocyte adenylate cyclase system. Our data would be in agreement with a possible direct interaction of protein kinase C with the catalytic subunit of adenylate cyclase system.
Phaneuf
S
S
Centre de Recherches de Biochimie Macromoléculaire, Institut National de la Santé, Montpellier, France.
Berta
P
P
Peuch
L P
LP
Haiech
J
J
Cavadore
J C
JC
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001011:Aorta / Q000378:metabolism; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D011493:Protein Kinase C; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate