Actions of a phorbol ester on factors regulating contraction in rabbit mesenteric artery.
The effects of 12-o-tetradecanoylphorbol-13-acetate (TPA) on isometric tension, unloaded shortening velocity determined using the slack test (Vmax), and phosphorylation of myosin light chain (MLC20) were investigated in intact and skinned muscle tissues of the rabbit mesenteric artery. In intact muscles exposed to 128 mM K+, the Vmax reached a maximum before the peak of the phasic component of contraction and reduced proportionally with changes in the amplitude of the subsequent tonic contraction. TPA (0.1 microM) enhanced to a greater extent the amplitude of the tonic than the phasic contraction. During the tonic phase, TPA enhanced the Vmax and amplitude of the contraction more than the phosphorylation of MLC20. In skinned muscles, Ca2+ (0.3-1.0 microM) increased the force, Vmax and MLC20 phosphorylation, in a dose dependent manner. The relation between any two of the above three parameters was always linear. TPA (0.1 microM) with phosphatidylserine (50 micrograms/ml) time-dependently increased the force and Vmax observed with 0.3-0.5 microM Ca2+. The relation between the force and Vmax shifted in the direction of that observed in the presence of high Ca2+, but in 0.5 microM Ca2+, TPA with phosphatidylserine showed little change in the phosphorylation of MLC20. As estimated from the actions of TPA, protein kinase C may contribute to activation of contractile proteins through MLC20 phosphorylation dependent and other regulatory processes.
Fujiwara
T
T
Department of Pharmacology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Itoh
T
T
Kubota
Y
Y
Kuriyama
H
H
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009218:Myosins / Q000378:metabolism; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D011493:Protein Kinase C; D009218:Myosins; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium