Immunochemical and Biochemical Distinction of Subtypes of Atrial Natriuretic Peptide Receptor1

The presence of subtypes of atrial natriuretic peptide (ANP) receptor has been demonstrated by examining the immunological features and ligand specificities of the receptors in various bovine tissues. The antibody probe used was the antiserum raised against the bovine lung ANP receptor, and the tissues examined for the possible presence of different types of ANP receptor were the lung, kidney, adrenal cortex, ovary, choroid plexus, and vascular tissues. When incubated with Triton extracts of these tissues, the antiserum strongly cross-reacted with the ovary, kidney, and choroid plexus receptors as well as the homologous lung receptor (type I). The adrenal and vascular receptors were recognized only weakly, however, suggesting the presence of distinct ANP receptors (type II). In support of this immunochemical subtyping, type I and type II receptors showed a marked difference in their ability to bind the ANP analog atriopeptin I (ANP5–25): type I receptors in the lung exhibited a moderate affinity for atriopeptin I with a KD of 10–9 M; however, type II receptors in adrenal and artery showed only a weak affinity for the analog with a KD of 10–9 M. Structural analysis of affinity-labeled ANP receptors by SDS-PAGE indicated that type I and type II receptors have similar disulfide-linked dimeric structures. These results suggest that the integrated response of the circulatory system to ANP depends on at least two populations of the dimeric receptor: type I receptors play a major functional role in the kidney where ANP exerts diuretic and natriuretic effects, whereas type II receptors appear to have the predominant role in the adrenal and vascular beds where aldosterone secretion and vascular tone are modulated, respectively, by ANP.