The proposed study will examine the cellular and subcellular effects and mechanisms of action of atrial natriuretic hormone. These studies will address the hypothesis that other hormones, as well as the cationic and oxidative milieu, affect the ANF- sensitive guanylate cyclase of glomerular cells and that some of these effects are exerted through changes in hormone-receptor binding, while others reflect a direct influence on the quanylate cyclase enzyme. An extension of the hypothesis, namely that some of the influences demonstrable in intact cells can also be demonstrated in isolated plasma membranes will be examined. The findings of the in vitro studies will be applied to two in vivo models of altered fluid and electrolyte homeostasis. This work will serve as a vehicle toward more intensive training in biomedical research within the Renal Division and the Department of Pharmacology at Washington University.