A synthetic pseudosubstrate peptide of protein kinase C inhibits the phorbol-12,13-dibutyrate effect on permeabilized coronary artery smooth muscle.
We have studied the effects of a synthetic peptide that is based on the autoinhibitory domain of protein kinase C on tension development in detergent-permeabilized coronary artery smooth muscle. This peptide inhibited two forms of protein kinase C that were isolated from the coronary artery media layer by hydroxylapatite chromatography, with apparent Ki values in the 5-8 microM range. Contractions induced by calcium in the permeabilized arteries were not affected by the peptide (30 microM). Potentiation of calcium-induced contractions by 1 microM phorbol-12,13-dibutyrate was partially inhibited by 10 microM peptide and was completely abolished by 30 microM peptide. These results indicate that phorbol-12,13-dibutyrate potentiates calcium-induced contractions of permeabilized coronary arteries by activation of protein kinase C, but activated protein kinase C is not a requirement for the induction of contractions by calcium alone.
Guthrie
T S
TS
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6600.
Tsuji
J
J
Wells
J N
JN
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003331:Coronary Vessels / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D003902:Detergents / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000302:isolation & purification / Q000494:pharmacology*; D013552:Swine
D003902:Detergents; D010446:Peptide Fragments; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C