Alteration in the myosin phosphorylation pattern of smooth muscle by phorbol ester.
Pretreatment with a high concentration of phorbol 12-myristate 13-acetate (PMA, 100 nM) increased the degree of tension and extent of myosin light chain (MLC20) phosphorylation in the K(+)-stimulated rabbit aortic artery. Pretreatment with 100 nM PMA did not alter the relationship between MLC20 phosphorylation and the tension seen with K+ stimulation in the initial phase and steady state of contraction. However, a low concentration of PMA (10 nM) potentiated only the MLC20 phosphorylation during the steady state of contraction with no effect on the tension. In contrast, the prostaglandin (PG) F2 alpha-induced tension development and the MLC20 phosphorylation were not affected by PMA pretreatment at both low and high concentrations. The inhibitory action of nifedipine on the K(+)-induced contraction was not affected by pretreatment with 100 nM PMA; the concentration producing half-maximal inhibition of nifedipine for the K(+)-induced contraction (33 nM) was the same as that of the K+ plus 100 nM PMA-induced contraction (32 nM). Our results suggest that PMA may increase the level of myosin light chain kinase-dependent MLC20 phosphorylation and the tension in the K(+)-stimulated artery, an effect which differs from that seen with increases in K+ concentrations. The regulatory mechanism for the contraction involving PGF2 alpha stimulation may differ from that seen in the case of K+ stimulation.
Seto
M
M
Biochemical Research Laboratory, Asahi Chemical Industry, Miyazaki, Japan.
Sasaki
Y
Y
Sasaki
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D009218:Myosins / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D010766:Phosphorylation; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors
D015237:Dinoprost; D009218:Myosins; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium