Effects of phorbol esters on contraction and protein kinase C activation in rabbit aorta.
This study investigates the relationship between the contractile efficacy of phorbol esters and their ability to activate protein kinase C in intact rabbit aorta. Phorbol dibutyrate (PDB) induced a maximal contraction approximately 3.5-fold greater than that to phorbol myristate acetate (PMA). The magnitude of maximal PDB- and PMA-induced contraction correlated with the magnitude of protein kinase C activation, as assessed by the decrease in cytosolic protein kinase C activity. KCl (60 mM) did not potentiate the PMA-induced decrease in cytosolic protein kinase C activity. These results suggest that the lack of efficacy of PMA is due to its inability to activate protein kinase C in the intact rabbit aorta. It is speculated that the different contractile efficacies of phorbol esters result from selective activation of protein kinase C isoforms, and that the amounts of these isoforms varies amongst vascular tissues.
Bazan
E
E
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, OH 45267-0575.
Campbell
A K
AK
Rapoport
R M
RM
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects*; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate