REGULATION OF SMOOTH MUSCLE CONTRACTION

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The goals of this research program are to elucidate some of the fundamental mechanisms that control contraction of coronary arteries and to gain insights into the mechanisms by which agents can relax smooth muscle. Specifically, this application proposes to determine if there is a role for protein kinase C in the control of smooth muscle contraction. The investigators will identify specific phosphorylation patterns that are due to protein kinase C activity and use these patterns to monitor the involvement of this kinase in the events that control contraction of smooth muscle. In addition, they will determine if the stimulant effects on smooth muscle of active phorbol esters are due to effects of these agents on protein kinase C. They will also develop a "state of the art" assay for diacylglycerol that is sensitive and accurate enough for use in small strips of smooth muscle. This assay will be utilized to investigate the possibility that changes in diaclyglycerol concentration control protein kinase C activity in smooth muscle, and to determine some of the factors that can alter diaclyglycerol content of intact smooth muscle.