Comparative molecular biology of natriuretic peptide receptors

Analysis of the mammalian natriuretic peptide system has established the pr esence of three types of receptors with distinct structural and functional features and tissue distributions. To clarify the physiological role of eac h subtype, we studied the natriuretic peptide system in animals with specia lized anatomical and physiological features. In this review, following a br ief description of the comparative and evolutionary aspects of the ligands, we will analyze the structure and distribution of natriuretic peptide rece ptors in lower vertebrates, as well as those of rats with essential and sal t-sensitive hypertension, and discuss the evolutionary aspects of the natri uretic peptide systems in mammals and fishes. Emphasis is placed on our ser ies of studies with eel receptors that revealed (i) interesting variations in the pattern of intra- and inter-molecular disulfide bonding; (ii) dense chondrocyte localization of NPR-C, which opened a new field of study for na triuretic peptides and bone metabolism; and (iii) the presence of a new rec eptor subtype, NPR-D, which is abundant in the brain and a member of the re ceptor subfamily with a short cytoplasmic C-terminal tail.