Differential activation by atrial and brain natriuretic peptides of two different receptor guanylate cyclases

Abstract

Alpha atrial natriuretic peptide (alpha-ANP) and brain natriuretic peptide are homologous polypeptide hormones involved in the regulation of fluid and electrolyte homeostasis. These two natriuretic peptides apparently share common receptors and stimulate the intracellular production of cyclic GMP as a second messenger. Molecular cloning has defined two types of natriuretic peptide receptors: the ANP-C receptor of relative molecular mass (Mr) 60-70,000 (60-70 K), which is not coupled to cGMP production and may function in the clearance of ANP and the ANP-A receptor of Mr 120-140 K, which is a membrane form of guanylate cyclase in which ligand binding to the extracellular domain activates the cytoplasmic domain of the enzyme. Here we report the cloning and expression of a second human natriuretic peptide-receptor guanylate cyclase, the ANP-B receptor. The ANP-B receptor is preferentially activated by porcine brain natriuretic peptide rather than human alpha-ANP, whereas the ANP-A receptor responds similarly to both natriuretic peptides. These observations may have important implications for our understanding of the central and peripheral control of cardiovascular homeostasis.

Aortic smooth muscle contains guanylate‐cyclase‐coupled 130‐kDa atrial natriuretic factor receptor as predominant receptor form

“…The actions of ANF at its target organs, including the kidney, adrenal gland, and vascular beds, are mediated by mem-brane-bound receptors that are coupled to guanylate cyclase. Guanylate-cyclase-coupled ANF receptors have been purified (Kuno et al, 1986;Takayanagi et al, 1987) and cloned from a number of sources (Chinkers et al, 1989;Chang et al, 1989;Lowe et al, 1989;Pandey and Singh, 1990;Koller et al, 1991). Analyses of the primary structures deduced from the cloned cDNA have suggested that the receptor consists of a single polypeptide chain with molecular mass of 120-140 kDa, containing an extracellular ANF binding domain, a single transmembrane sequence, and an intracellular guanylate cyclase domain.…”

Characterization of natriuretic peptide receptors in the rat parotid

“…The results of cyclic GMP accumulation by CNP and of RT-PCR revealed that the GC-B receptor is present in the rat parotid gland. The GC-B receptor has been originally identified in the human placenta (22) and rat brain (5) and has been detected in many tissues and cells such as pituitary gland, adrenal medulla (23) and cultured vascular smooth muscle cells (24). Recent reports have indicated the paracrine nature of CNP particularly in blood vessels.…”

The Regulation and Physiological Roles of the Guanylyl Cyclase Receptors.

“…GC-A and GC-B are expressed widely but not equally throughout the body [61][62][63][64][65][66][67][68][69][70][71][72][73][74][75][76]. GC-A is most abundant in the cardiovascular system (kidney, heart, and aorta) [61][62][63]65] whereas GC-B expression is particularly high (greater than GC-A) in the cerebellum, pituitary gland, pineal gland, and growth plate of bone [61,[72][73][74].…”