The guanylyl cyclase family of natriuretic peptide receptors

Guanylyl cyclases are cytoplasmic and membrane-associated enzymes that catalyze the conversion of GTP to cyclic GMP, an intracellular signaling molecule. Molecular cloning has identified a multigene family encoding both soluble and particulate forms of the enzymes. Diffusible agents such as nitric oxide and carbon monoxide activate the soluble guanylyl cyclases. The particulate members of the family share a characteristic domain arrangement, with a single transmembrane span separating a variable extracellular ligand-binding domain from a conserved intracellular regulatory and cyclase catalytic domain. Seven members of the particulate guanylyl cyclase family have been identified, and they include the receptors for natriuretic peptides and Escherichia coli heat-stable enterotoxin. Recently, animal models have been developed to study the role of natriuretic peptides and their guanylyl cyclase-coupled receptors in renal and cardiovascular physiology.