Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A.
Besides soluble guanylyl cyclase (GC), the receptor for NO, there are at least seven plasma membrane enzymes that synthesize the second-messenger cGMP. All membrane GCs (GC-A through GC-G) share a basic topology, which consists of an extracellular ligand binding domain, a short transmembrane region, and an intracellular domain that contains the catalytic (GC) region. Although the presence of the extracellular domain suggests that all these enzymes function as receptors, specific ligands have been identified for only three of them (GC-A through GC-C). GC-A mediates the endocrine effects of atrial and B-type natriuretic peptides regulating arterial blood pressure and volume homeostasis and also local antihypertrophic actions in the heart. GC-B is a specific receptor for C-type natriuretic peptide, having more of a paracrine function in vascular regeneration and endochondral ossification. GC-C mediates the effects of guanylin and uroguanylin on intestinal electrolyte and water transport and on epithelial cell growth and differentiation. GC-E and GC-F are colocalized within the same photoreceptor cells of the retina and have an important role in phototransduction. Finally, the functions of GC-D (located in the olfactory neuroepithelium) and GC-G (expressed in highest amounts in lung, intestine, and skeletal muscle) are completely unknown. This review discusses the structure and functions of membrane GCs, with special emphasis on the physiological endocrine and cardiac functions of GC-A, the regulation of hormone-dependent GC-A activity, and the relevance of alterations of the atrial natriuretic peptide/GC-A system to cardiovascular diseases.
Kuhn
Michaela
M
Institute of Pharmacology and Toxicology, Universitätsklinikum Münster, Domagkstrasse 12, D-48149 Münster, Germany. mkuhn@uni-muenster.de
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008322:Mammals; D020097:Natriuretic Peptide, Brain; D017434:Protein Structure, Tertiary; D051381:Rats; D017461:Receptors, Atrial Natriuretic Factor / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*
D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A