Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultures of renal cells from human or animal origins have allowed the modes of action and the degradation pathways of atrial natriuretic factor (ANF) to be characterized. Human glomerular mesangial and epithelial cells possess ANF receptors of both types, only clearance receptors (C) in mesangial cells, receptors with guanylate cyclase activity (A) and C receptors in epithelial cells which are, in addition, equipped with ectoenzymes rapidly degrading extracellular ANF. Epithelial cells which have been stimulated by ANF secrete cyclic guanosine monophosphate (cGMP) at their apical side. Vascular smooth muscle cells prepared from the rabbit renal cortex also possess A receptors of high affinity and C receptors. Neutral endopeptidase (NEP), an enzyme of which ANF is a specific substrate in the kidney, is expressed at the cell surface. Its expression is inhibited by factors present in the serum and is increased by glucocorticoids. Principal cells of the collecting duct are also a target for ANF via A and C receptors. Taken together, these studies demonstrate that the kidneys are sites both for the physiological effects and the degradation of ANF. Production of cGMP results in vasodilation in the renal cortex, increase of glomerular filtration rate and decrease of sodium reabsorption in the collecting duct. Degradation of ANF occurs via two different ways, its conversion into inactive peptides by NEP and its internalization after binding to C receptors.
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PMID:[Mechanism of action and catabolism of atrial natriuretic factor in cultured human and animal kidney cells]. 146 27

The physiology, the pharmacology and the biochemistry of the atrial natriuretique factor (ANF) have been investigated and documented by numerous studies and works since its discovery and cloning ten years ago. More recently, the physiopathological aspect of ANF biosynthesis and secretion by the whole heart during overload and congestive heart failure was reported in experimental models and in human patients. Moreover the cyclic GMP which is the ANF second messenger, egressed from endothelial cells, was correlated with the production of ANF. Therefore the activation of heart endocrine function from ANF gene over-expression to peripheral cyclic GMP appeared as an independent prognosis indicator in congestive heart failure. Two types of ANF receptors have been recently cloned. One is the particulate guanylate cyclase, the second is a clearance receptor involved in the endocytosis and lysozomial degradation of ANF in target cells. Neutral endopeptidase, an ectoenzyme present in different tissues and particularly in the kidney is also capable to cleave ANF in unefficient peptide. The blockade of ANF metabolism by clearance receptor antagonists and neutral endopeptidase inhibitor potentializes the biological effect of exogenous and endogenous ANF particularly on the renal function. This approach of ANF metabolism-inhibition opens new ways on the future of ANF in cardiovascular therapeutic.
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PMID:[Atrial natriuretic factor. Current data and future perspectives]. 217 42

Neutral endopeptidase (NEP, metallo-endopeptidase EC 3.4.24.11; enkephalinase, neprilysin, CD10, CALLA) represents a major regulator of bioactivity of natriuretic peptides. C-type natriuretic peptide (CNP) is present in high levels in epididymis and seminal plasma. However, detailed expression pattern and CNP-related function of NEP in the epididymis are unknown. Comparison of NEP protein levels in various organs revealed an extremely high expression in human and mouse epididymis. NEP was localized exclusively to apical (luminal) parts of epithelial cells. In man, strong NEP-immunoreactivity was associated with epithelia of efferent ducts and the epididymal duct including stereocilia. Segment-by-segment analysis in mouse revealed a distinct distribution along the epididymal duct. We also found the CNP receptor guanylyl cyclase B (GC-B) in epithelial cells of the epididymal duct. Two different NEP inhibitors decreased CNP degradation and increased CNP/GC-B-induced cGMP production by epididymal membranes, suggesting a functional involvement of NEP. Data indicate an important, previously neglected, role of NEP for regulation of luminal factors in the epididymis and suggest a novel role for CNP/GC-B in the epididymal epithelium, presumably in context of local water balance.
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PMID:Neutral endopeptidase (CD10) is abundantly expressed in the epididymis and localized to a distinct population of epithelial cells--its relevance for CNP degradation. 2409 62