Phorbol diesters alter the contractile responses of porcine coronary artery.
We have studied the effects of activators of the Ca++- and phospholipid-dependent enzyme protein kinase C on isometric tension development by both intact and skinned coronary artery strips. The intact strips contracted upon incubation with 12-O-tetradecanoylphorbol-13-acetate. 12-O-tetradecanoylphorbol-13-acetate produced a leftward shift in the concentration-response relationship for contraction of the tissues by K+, histamine and norepinephrine. Phorbol-12,13-dibutyrate elicited contraction of detergent-skinned artery strips when the free Ca++ concentration in the bathing media was 0.1 microM or greater. This effect was diminished greatly in the presence of polymyxin B, a putative inhibitor of protein kinase C. Phorbol-12,13-dibutyrate shifted the Ca++ concentration-tension response relationship for the skinned tissue to the left. These results are consistent with a role for protein kinase C in regulating the contractile responses of coronary arterial smooth muscle to a variety of stimuli, at least in part by increasing the sensitivity of the contractile apparatus to Ca++.
Miller
J R
JR
Hawkins
D J
DJ
Wells
J N
JN
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D011112:Polymyxin B / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D006632:Histamine; D011493:Protein Kinase C; D011112:Polymyxin B; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine