Natriuretic peptides receptors: Molecular biology, phisiology and clinical implication

Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine/autocrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. The cellular responsiveness of natriuretic peptides is manifested through specific cell surface receptors widely spread in different target tissues. In human three single membrane-spanning natriuretic peptide receptors have been identified. Two of this natriuretic peptide receptor type A and atriuretic peptide receptor type B, are transmembrane guanylyl cyclases, enzymes that catalyze the synthesis of cyclic guanosine monophosphate. One natriuretic peptide receptor type C, lacks intrinsic enzymatic activity and controls the local concentrations of natriuretic peptides through constitutive receptor-mediated internalization and degradation. Natriuretic peptide receptor type A has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate guanylyl cyclase. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, kinase homology domain phosphorylation and adenosine triphosphate binding. Finally gene knockout and genetic segregation studies have provided strong evidence for the importance of natriuretic peptide receptor type A in the regulation of blood pressure and heart and renal functions. This chapter will focus on the physiology and molecular biology of natriuretic peptide receptor ; also we discussing their role in cardiovascular disease.