HUMAN PLACENTAL ATRIAL NATRIURETIC FACTOR RECEPTORS

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Atrial natriuretic factor (ANF), a recently discovered polypeptide hormone, is one of the most potent naturally occurring natriuretic and diuretic agents. By analogy to other hormones, its cellular effects are probably mediated by ANF-receptor interactions. The aims of this research are to characterize biochemically, physicochemically, and immunologically ANF receptor from human placenta. We will also characterize the ANF-induced phosphorylation of an endogenous substrate which we have recently observed in placental membranes and establish its relationship to the receptor. We will purify the receptor by affinity chromatography; establish optimal conditions and structural requirements for binding of the hormone to its receptors; determine its physicochemical structure; investigate the possibility of multiple binding site & prepare antibodies against receptor protein. Availability of purified receptor and antireceptor antibodies will enable us to fulfill our long-term goals of determining tissue, cellular, and subcellular distribution of atrial natriuretic factor receptors; elucidating its biosynthesis in human tissues; detecting structural differences in it associated with physiological or pathophysiological conditions such as pregnancies complicated with hypertension, and perhaps intervening therapeutically in the pathogenic process to which it contributes.