The proposed research is in three areas: 1) cellular calcium metabolism; 2) the messenger functions of calciumand cAMP in hormone action; and 3) the mechanism of sensitivity modulation both at the cellular and moleculr level. Investigations of cellular calcium metabolism will include: a) a systematic search or cellular calsium binding protiens, an their isolation and characterization; b) study of the control of mitochondrial calcium exchange; c) studies of the effect of membrane structural changes upon the activity of the plasma membrane calcium pump in rat and human eryghrocytes; and d) and investigation into the mechanisms responsible for the altered metabolism of cell calcium in red cells from patients with Duchene's Muscular Dystrophy, Sickle Cell Anemia, and rats with hypothyroidisim. Studies of Ca2+ cAMP messenger function will focus on the interrelated roles of tese messenger in the hormonal and ionic control of aldosterone secretion by the adrenal glomerulosa, and their roles in mediating the actions of serotonin and cholera toxin on intestinal fluid secretion. Studies of sensitivity modulation will concentrate on defining the mechanisms by which a standard neurogenic stimulus, and, the relationship between the cAMP-dependent phosphorylation of myosin light chain kinase, and the activaton of this enzyme by calcium-calmodulin. Each of these reearch projects focuses on an aspect of the problem of defining the messenger function of calcium in hormone activaiton and the relationship between Ca2+ and cAMP in regulating cell function.
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