title: Biochemistry and physiology of the natriuretic peptide receptor guanylyl cyclases.
abstract: Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), 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 GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology.
authors.affiliation: Research Centre, Centre hospitalier de l 'Université de Montréal, Montreal, Quebec, Canada. johanne.tremblay@umontreal.ca
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.forename: Richard
authors.initials: R
authors.lastname: Desjardins
authors.forename: David
authors.initials: D
authors.lastname: Hum
authors.forename: Jolanta
authors.initials: J
authors.lastname: Gutkowska
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure; D001810:Blood Volume; D009202:Cardiomyopathies / Q000378:metabolism; D015536:Down-Regulation; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007527:Isoenzymes; D018000:Receptors, Peptide; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled