Rembold C M, Murphy R A
Department of Physiology, University of Virginia, School of Medicine, Charlottesville 22908.
Am J Physiol. 1988 Dec;255(6 Pt 1):C719-23. doi: 10.1152/ajpcell.1988.255.6.C719.
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.
佛波酯是蛋白激酶C的强效激活剂，可使动脉平滑肌产生缓慢收缩。此类观察结果促使人们提出，蛋白激酶C可能在收缩过程中具有直接调节功能。在本文中，我们提供证据表明，依赖于[Ca2+]的肌球蛋白轻链磷酸化是低剂量佛波酯诱导收缩以及高剂量佛波酯刺激后力量产生过程中收缩的原因。低剂量佛波二丁酸酯诱导的肌浆[Ca2+]、肌球蛋白磷酸化和稳态应力之间的关系与收缩激动剂所观察到的相似。然而，长时间暴露于高剂量佛波二丁酸酯会诱导高应力和磷酸化升高，而这与水母发光蛋白估计的[Ca2+]升高无关。我们的结果表明，佛波酯可增加肌浆[Ca2+]，由此导致的肌球蛋白磷酸化增加在数量上解释了收缩现象。
