Molecular Pharmacology of Myosin Light Chain Phosphorylation of Smooth Muscle and Nonmuscle Cells

Abstract

This chapter focuses on the molecular pharmacology of myosin light chain phosphorylation of smooth muscle and nonmuscle cells. Myosin light chain phosphorylation of smooth muscle and nonmuscle cells are catalyzed by both Ca, calmodulin dependent myosin light chain kinase, and protein kinase C. Purified smooth muscle myosin light chain kinase is inactivated by incubation with 5′- p -fluorosulfonylbenzyol adenosine, at 30°C. To clarify the relationship between the chemical structure and potency in inhibition of ML-9, and its derivatives, iodine-, bromine- and chlorine-substituted derivative at the naphthalene ring were examined for their inhibitory effect on myosin light chain kinase. Protein phosphorylation is an established major general mechanism by which intracellular events in mammalian tissues are controlled by external physiological stimuli, but its effects are indirect and interrelationships among each protein phosphorylation system are complex. Diverse Ca 2+ -dependent cellular processes such as smooth muscle contraction and nonmuscle cell secretion are thought to be regulated by Ca 2+ dependent protein phosphorylation systems. To investigate the quantitative aspects and molecular mechanisms of the calcium messenger system, the potent and specific inhibitors will be synthesized in studies on this cellular regulatory system.