Analysis of the mammalian natriuretic peptide system has established the presence of three types of receptors with distinct structural and functional features and tissue distributions. To clarify the physiological role of each subtype, we studied the natriuretic peptide system in animals with specialized anatomical and physiological features. In this review, following a brief description of the comparative and evolutionary aspects of the ligands, we will analyze the structure and distribution of natriuretic peptide receptors in lower vertebrates, as well as those of rats with essential and salt-sensitive hypertension, and discuss the evolutionary aspects of the natriuretic peptide systems in mammals and fishes. Emphasis is placed on our series 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 natriuretic peptides and bone metabolism; and (iii) the presence of a new receptor subtype, NPR-D, which is abundant in the brain and a member of the receptor subfamily with a short cytoplasmic C-terminal tail.
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