Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simplified procedure for the purification of the extracellular protease of Pseudomonas fragi was developed. The enzyme was isolated from a derepressed mutant producing 40 times the enzyme level of the parental organism. It was collected from culture filtrates by ammonium sulfate precipitation, and it was obtained in pure form by single chromatography on a column of diethylaminoethyl cellulose. The protease had a molecular weight of 52,000 as estimated by sodium dodecyl sulfate-gel electrophoresis and had properties of a classical neutral endopeptidase with the exception of its substrate specificity. Mutants of P. fragi producing proteases of altered substrate specificities were isolated from plates containing elastin as the sole carbon source. The SP-Sephadex elution patterns of enzymes extracted from each mutant examined were complex, suggesting that either the enzyme was autodigested or several active forms could be generated from a common precursor. The substrate specificities of the mutant enzymes were different from that produced by the parental strain.
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PMID:Isolation and properties of the protease from the wild-type and mutant strains of Pseudomonas fragi. 4 39

The proteins of microvilli prepared from pig kidney were analysed by polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate. The typical pattern stained for protein revealed five major bands, four of which also stained for carbohydrate, and about 15 minor bands. For descriptive purposes the bands were designated numerically by their apparent molecular weights (X10(-3). Well-characterized proteins were identified with four of the five major bands. Dipeptidyl peptidase IV, a serine proteinase that may be specifically labelled with di-isopropyl [32P]phosphorofluoridate, was assigned to band 130. Aminopeptidase M was assigned to band 160, though when released from the membrane by a proteinase, this protein comprises three polypeptides each of lower apparent molecular weight than the native enzyme. Neutral endopeptidase can be assigned to band 95 and actin to band 42. The fifth major band (180) is an extrinsic glycoprotein that has not been identified with any microvillus enzyme activity. These four proteins contribute 21% of the microvillus-membrane protein. Kidney microvillus actin was characterized by a variety of properties and was similar to muscle actin. A computer analysis of the gel pattern indicates that it comprises 9.0% of the microvillus protein. Myosin is not present in the microvillus, but another protein associated with band 95, with properties that distinguish it from neutral endopeptidase, was tentatively identified as alpha-actinin. Alkaline phosphatase was identified as a monomeric polypeptide with an apparent molecular weight of 80000; it is a minor protein of the microvillus and is not discernible as a discrete band in the gel pattern. These and other results permit a model of the organization of the microvillus protein to be suggested. The computer program used has been deposited as Supplementary Publication SUP 50070 (12 pages) at the British Library Lending Division, Boston Spa. Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1976) 153,5.
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PMID:Proteins of the kidney microvillus membrane. Identification of subunits after sodium dodecylsullphate/polyacrylamide-gel electrophoresis. 13 63

Antibodies raised in rabbits to detergent-solubilized pig kidney microvillar proteins have been used to investigate the membrane hydrolases by crossed immunoelectrophoresis. Eight enzymes were detected by specific staining methods: aminopeptidase M, dipeptidylpeptidase IV, neutral endopeptidase, aminopeptidase A, carboxypeptidase P, gamma-glutamyltransferase, trehalase and phosphodiesterase I. The mobility of all these enzymes, with the exception of trehalase and neutral endopeptidase, was increased by treatment of the detergent-solubilized preparation with papain. The difference between the detergent and proteinase forms of these enzymes is attributed to the removal of a small, non-antigenic peptide to which detergent is bound in significant quantities. This interpretation was further supported by experiments in which the microvillus fraction was labelled with an intramembrane photolabelling reagent, 1-azido-4-[125I]iodobenzene. After photolysis, the radioactivity in the membrane could be solubilized by detergent treatment but not by papain treatment. Radioautography after crossed charge-shift immunoelectrophoresis showed a good correlation between charge-shift (signifying the presence of detergent bound to a hydrophobic domain) and the presence of the label.
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PMID:Proteins of the kidney microvillar membrane. Immunoelectrophoretic analysis of the membrane hydrolases: identification and resolution of the detergent- and proteinase-solubilized forms. 48 90

The membrane of kidney microvilli is richly endowed with peptidases. Present information is that there are at least eight examples located in this membrane. Three of the group are known to be among the major proteins that can be identified by dodecyl sulphate electrophoresis of the purified microvillus fraction. These three peptidases, aminopeptidase M, serine peptidase (dipeptidyl peptidase IV) and neutral endopeptidase can be labelled by lactoperoxidase iodination from either the luminal or the inner surfaces of the membrane, a result consistent with the view that the polypeptide chains span the microvillus membrane. The serine peptidase has been purified by two methods, permitting a comparison of the detergent-released and proteinase-released forms. The two forms differ in the presence and absence of the hydrophobic anchor that secures the enzyme to the membrane. Preliminary studies support the view that this hydrophobic domain is relatively small and that it includes the N-terminal region of the polypeptide chain.
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PMID:Kidney microvillus peptidases--are they transmembrane proteins? 61 79

Renal tumours were induced in dietary-primed rats by injection of dimethylnitrosamine. Control and tumour tissue was excised at varying periods and maintained in short-term organ culture in the presence of 3H- or 14C-fucose. The plasma membranes were then isolated, and the isotopic profiles of normal kidney and renal tumour membrane proteins were established, using polyacrylamide-gel electrophoresis in dodecyl sulphate. Several fucose-containing glycoproteins of the plasma membranes were found to alter upon neoplastic transformation: 4 increased and 3 decreased. The probable identity of 2 of these proteins is indicated: alpha-foetoprotein is one of the glycoproteins which increased, whereas neutral endopeptidase decreased in the tumour membranes. Fluorescein-labelled lectin binding by the kidney tissue was also found to alter upon transformation. The most marked changes were an increase in sialic acid (neuraminidase-sensitive) and galactosamine (Ricinus communis agglutinin Type I) in the nuclei of some neoplastic cells and some hyperplastic-tubule cells.
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PMID:Saccharide alterations in rat kidney associated with malignant transformation by injection of dimethylnitrosamine. 65

The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute inhibition of endopeptidase 24.11 in essential hypertension: SCH 34826 enhances atrial natriuretic peptide and natriuresis without lowering blood pressure. 128 Jul 35

1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum.
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PMID:A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder. 128 72

We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.
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PMID:Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs. 128 24

Atrial natriuretic peptide (ANP) is degraded by neutral endopeptidase (NEP) mainly in the proximal tubule of the kidneys. We studied the effects of retrothiorphan, a potent and highly specific NEP inhibitor on renal function and blood pressure (BP). A 25-mg/kg bolus injection (group bolus), or bolus injection plus infusion 25 mg/kg + 25 mg/kg/h (group infusion), was given to conscious normotensive Wistar and hypertensive DOCA-salt rats. Bolus and infusion produced increases in diuresis (110 +/- 15 vs. 103 +/- 15 vs. 42 +/- 9 microliters/min) and natriuresis (10.6 +/- 3.0 vs. 7.0 +/- 1.0 vs. 5.4 +/- 1.0 mumol/min) in normotensive rats, with a maximum change at 30 min. Change in kaliuresis was not significant. These renal effects were associated with nonsignificant increases in urinary cyclic GMP and ANP. Arterial pressure and heart rate (HR) were not affected. Bolus or infusion of retrothiorphan also induced increases in diuresis (92 +/- 16 vs. 124 +/- 13 vs. 38 +/- 6 microliters/min) and natriuresis (10.3 +/- 2.0 vs. 12.5 +/- 1.0 vs. 5.0 +/- 1.0 mumol/min) in DOCA-salt hypertensive rats, with a maximum change at 30 min. The changes in diuresis and natriuresis induced by retrothiorphan were correlated with a significant increase in urinary cyclic GMP excretion (r = 0.89, p < 0.001 and r = 0.91, p < 0.001). Urinary ANP did not change in controls but significantly increased in the treated rats; urinary immunoreactive bradykinin (BK) also tended to increase. Plasma ANP and hematocrit did not change after retrothiorphan, but plasma cyclic GMP increased significantly after infusion. Only infusion caused a decrease in arterial pressure in DOCA-salt rats (-20 mm Hg at 120 min). Renal clearance studies in DOCA-salt rats showed that retrothiorphan has a transient effect on renal hemodynamics, with increases in glomerular filtration and renal blood flow (RBF) and a decrease in renal vascular resistance (RVR). Its renal action was also tubular, with an increase in fractional sodium excretion. We also compared the effects of retrothiorphan in normotensive Brown-Norway kininogen-deficient rats (BN-Kat) and DOCA-salt hypertensive kininogen-deficient rats. The NEP inhibitor induced increases in diuresis and natriuresis in both groups, with increased urinary cyclic GMP. Urinary immunoreactive BK did not change significantly in normotensive or DOCA-salt hypertensive kininogen-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of the selective neutral endopeptidase inhibitor, retrothiorphan, on renal function and blood pressure in conscious normotensive Wistar and hypertensive DOCA-salt rats. 128 84

The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA.
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PMID:Bradykinin degrading activity in cultured human endothelial cells. 128 24


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