Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions.
Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The mammalian members are atrial natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, and possibly osteocrin/musclin. Three single membrane-spanning natriuretic peptide receptors (NPRs) have been identified. Two, NPR-A/GC-A/NPR1 and NPR-B/GC-B/NPR2, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cGMP. One, NPR-C/NPR3, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Single allele-inactivating mutations in the promoter of human NPR-A are associated with hypertension and heart failure, whereas homozygous inactivating mutations in human NPR-B cause a form of short-limbed dwarfism known as acromesomelic dysplasia type Maroteaux. The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described.
Potter
Lincoln R
LR
Department of Biochemistry, Molecular Biology, and Biophysics, 6-155 Jackson Hall, 321 Church Street SE, University of Minnesota, Minneapolis, Minnesota 55455, USA. potter@umn.edu
Abbey-Hosch
Sarah
S
Dickey
Deborah M
DM
D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D006130:Growth Disorders / Q000188:drug therapy; D006331:Heart Diseases / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D045265:Natriuretic Peptides / Q000502:physiology* / Q000627:therapeutic use; D009765:Obesity / Q000188:drug therapy; D017434:Protein Structure, Tertiary / Q000502:physiology; D020239:Receptor Cross-Talk / Q000502:physiology; D018000:Receptors, Peptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D045265:Natriuretic Peptides; D018000:Receptors, Peptide; D006152:Cyclic GMP