This research project focuses on aspects of calcium channel function. It will provide data to characterize the methylation of phospholipeds by S-adenosyl-L-methionine in membranes of vascular smooth muscle. It will characterize the resulting modulation of membrane fluidity, calcium channels, signal transmission, pharmacologic activity fo calcium channel antagonists and vascular contraction. Isolated arterial strips and isolated membrane vesicles will be employed. The interaction of phospholipid methylation with signal transduction associated with receptor activated hydrolysis of triphosphosphosphatidylinositol and the mobilization of intracellular calcium will be studied. The regulation of and role of phospholipid methylation in SHR and DOCa hypertension will be investigated. Phospholipid methylation also will be studied in isolated cardiac membranes. In isolated vascular smooth muscle cells, the relation of phospholipid methylation activity to cell proliferation and the protective effect of calcium channel blocking agents in cell injury will be examined.
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