Human neutral endopeptidase

C. Oefner, A. D Arcy, M. Hennig, F. K. Winkler, G. E. Dale, Structure of Human Neutral Endopeptidase Complexed with Phosphoramidon , Protein Data Bank ID ldmt, 1999 (H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov, P. E. Bourne, The Protein Data Bank , Nucleic Acids Res. 2000, 28, 235-242). 

Table 2. Pairwise comparison of the topology and sequence of members of the long spacer family. Primary sequences for human Angiotensin Converting Enzyme [57], Botulinum Neurotoxin A [58], human Neutral Endopeptidase [59] have been used in the pairwise sequence comparison. Legend as in Table 1.

Cohen AJ, Bunn PA, Franklin W, Magill-Solc C, Hartmann C, Helfrich B, Gilman L, Folkvord J, Helm K, Miller YE (1996) Neutral endopeptidase Variable expression in human lung, inactivation in lung cancer, and modulation of peptide-induced calcium flux. Cancer Res 56(4) 831-839. 

The generally accepted view is that ECE is a metalloprotease. Enzymes of this type have been isolated from a variety of tissue sources including cultured endothelial cells [65], vascular smooth muscle [66], human umbilical vein [67] and human brain [68], and have been characterized as neutral endopeptidases sensitive to phosphoramidon. Several groups have demonstrated an endothelial cell derived ECE which is active at neutral pH and inhibited by phosphoramidon and other metal chelators, but not by... 

Cheung, D., Bel, E.H., Den Hartigh, J. etal. (1992). The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo. Am. Rev. Respir. Dis. 145, 1275-1280. 

Goctzl, E.J., Sreedharan, S.P., Turck, C.W. etal. (1989). Preferential cleavage of amino- and carboxyl-terminal oligopeptides from vasoactive intestinal polypeptide by human recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11). Biochem. Biophys. Res. Commun. 158, 850-854. 

Borson, D.B. and Gruenert, D.C. (1991). Glucocorticoids induce neutral endopeptidase in transformed human tracheal epithelial cells. Am. J. Physiol. (Lung Cell. Mol. Physiol.) 260, L83-L89. 

Dragovic, T. et al. (1994) Increased expression of neprilysin (neutral endopeptidase 24.11) in rat and human hepatocellular carcinomas. Lab. Invest., 70.107-113. 

Ino K, Suzuki T, Uehara C, et al. The exptession and localization of neutral endopeptidase 24.11/CDlO in human gestational trophoblastic diseases. Lab Invest. 2000 80 1729-1738. 

Werfel T, Sonntag G, Weber MH, Gotze O Rapid increases in the membrane expression of neutral endopeptidase (CDIO), aminopeptidase N (CD13), tyrosine phosphatase (CD45), and Fc gamma-RIII (CD 16) upon stimulation of human peripheral leukocytes with human C5a. J Immunol 1991 ... 

Painter, R.G., Dukes, R., Sullivan, J., Carter, R., Erdos, E.G. and Johnson, A.R. (1988). Function of neutral endopeptidase on the cell membrane of human neutrophils./. Biol. Chem. 263, 9456-9461. 

ANP is a polypeptide hormone that is secreted in large quantities by the atrial portion of the heart and from a variety of other mammalian cell types. It exerts many of its actions via activation of particulate guanylate cyclase [16, 134]. ANP is present in human follicular fluids [163] and specific ANP receptors have been identified in human spermatozoa [144]. Sperm chemotaxis to ANP was demonstrated by sperm accumulation in capillaries with ascending [6] and descending [192] gradients and by choice assays [192] (Table 4). It is not yet known whether ANP is involved in sperm chemotaxis in vivo and whether the physiological chemoattractant for human spermatozoa is an ANP-like substance. Since chemotaxis to ANP at physiological concentrations can be observed only in the presence of a neutral endopeptidase inhibitor such... 

We observed no undesired activities on the human hERG channel and no hints for genotoxicity in the micronucleus and for mutagenicity in the AMES II test system. In addition, this compound had low log D and PSA values and a high solubility. This compound had a limited cell permeability as measured in the Caco-2 assay. Regarding selectivity, 9b showed a submicromolar activity on neutral endopeptidase (NEP), which is another major peptidase involved in bradyki-nin metabolism [25,39]. 

Enzyme Endothelin converting enzyme (human) Activity IC5o= 1.1 m-M Enzyme Neutral endopeptidase (human) Activity 1650 = 1.1 M... 

McDowell G, Nicholls DP. The therapeutic potential of can-doxatril, a neutral endopeptidase inhibitor, in humans Cardi-ovasc. Drug Rev. 2000 18(4) 259 270. 

---