[Ca2+]-dependent myosin phosphorylation in phorbol diester stimulated smooth muscle contraction.
Phorbol diesters, potent activators of protein kinase C, can produce a slow contraction in arterial smooth muscle. Such observations have prompted proposals that protein kinase C may have direct regulatory functions in contraction. In this paper, we present evidence that [Ca2+]-dependent myosin light chain phosphorylation is responsible for the contraction induced by low-dose phorbol diester and during force development in response to high-dose phorbol diester stimulation. The relationships between myoplasmic [Ca2+], myosin phosphorylation, and steady-state stress induced by low-dose phorbol dibutyrate were similar to those observed with contractile agonists. However, prolonged exposure to high-dose phorbol dibutyrate induced high stress with elevated phosphorylation that was not associated with elevations in aequorin-estimated [Ca2+]. Our results suggest that phorbol diesters can increase myoplasmic [Ca2+], and the resulting increase in myosin phosphorylation quantitatively explains the contraction.
Rembold
C M
CM
Department of Physiology, University of Virginia, School of Medicine, Charlottesville 22908.
Murphy
R A
RA
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D015879:Myosin Subfragments; D009218:Myosins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010766:Phosphorylation; D012016:Reference Values; D013552:Swine
D015879:Myosin Subfragments; D010446:Peptide Fragments; D015240:Phorbol 12,13-Dibutyrate; D009218:Myosins; D002118:Calcium