Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion.
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PMID:Effect of inhibition of peptidase activity on distribution of intrarenal blood flow. 16 95

2200-fold purified homogenous preparation of carboxycathepsin (peptidyl-dipeptidase) is isolated from bovine lung. The enzyme isolated converts angiotensine I into angiotensine II and distroys bradikinin. It is active in neutral medium, is activated by chloride ion and is inhibited by EDTA and Middle Asian snakes venom. The molecular weight of the enzyme is 180 000-190 000 as estimated by means of polyacrylamide gel electrophoresis, its isoelectric point is 4.48-4.53. The comparison of properties and specificity of carboxycathepsin from bovine lung and kidney draws to the conclusion that both enzymes are identical.
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PMID:[Isolation and properties of carboxycathepsin (peptidyl-dipeptidase) from bovine lung tissue]. 17 20

An effect of carboxycathepsin (peptidyl-dipeptidase EC 3.4.15.1) from bovine kidney on bradikinine was studied. The bradikinine activity was determined by monitoring the rat uterine horn retraction. Carboxycathepsin caused rapid inactivation of bradikinine (440-500 mcg of bradikinine/mg/min). The rate of bradikinine inactivation depended on the incubation time, content of the enzyme and substrate in the samples. In presence of EDTA carboxycathepsin did not inactivate bradikinine.
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PMID:[Effect of carboxycathepsin on biological activity of bradykinin]. 19 87

By means of high voltage electrophoresis experiments it could be demonstrated that the dipeptide hydrolase present in the plasma of Bothrops jararaca is similar to the angiotensin I converting enzyme of human plasma. Therefore, angiotensin I can be considered as a probable natural substrate for this potent snake peptidase in contrast to bradykinin, which is excluded in that case, since this snake plasma was previously found to be deficient in intrinsic kinin releasing system. On the other hand, the presence of angiotensinase activity in this snake plasma could also be demonstrated. Through the pharmacological comparison of angiotensin II with the pressor peptide released from the Bothrops jararaca plasma by chymotrypsin, an indirect indication of the presence of angiotensinogen in the plasma of this reptile was obtained.
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PMID:Components of the renin-angiotensin system in the plasma of Bothrops jararaca. 20 19

Endothelial cells in tissue culture degrade bradykinin and convert angiotensin I to angiotensin II. These are both functions of a single dipeptidyl hydrolase, angiotensin converting enzyme. Monolayer cultures were prepared from human, rabbit, pig, and calf vessels. Angiotensin converting enzyme activity was assessed by adding either bradykinin or angiotensin I to the cells in culture flasks, and measuring residual peptide over time by radioimmunoassay. Peptide degradation was inhibited by the specific converting enzyme inhibitor, SQ 20881. The flasks were equilibrated with varying hypoxic gas mixtures: hypoxia rapidly (less than 2 min) decreased enzyme activity and room air restored it as rapidly. The extent to which activity was reduced was a direct function of PO2 (r = 0.93, P less than 0.001), and there was no enzyme activity below a PO2 of 30 mm Hg. Four preparations were studied with respect to decrease in enzyme activity by hypoxia: (a) intact cells in monolayer, (b) sonicated cells, (c) sonicated cells from which converting enzyme was partially dissolved by a detergent, and (d) purified converting enzyme. Hypoxia had progressively less of an inhibiting effect on the enzyme activity of the preparations as the degree of cell integrity decreased. Hypoxia inhibits angiotensin converting enzyme activity in cultured endothelial cells, but the effect of hypoxia is not on the enzyme per se, but appears to be a unique characteristic of the endothelial cell.
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PMID:Inhibition of angiotensin converting enzyme activity in cultured endothelial cells by hypoxia. 391 85

1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil. 2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine. 3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal L-Leu-Gly hydrolase activity. 4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.
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PMID:Changes in absorptive and peptide hydrolase activities in rat small intestine after administration of 5-fluorouracil. 63 72

A dipeptide hydrolase from the brush border of guinea-pig intestinal mucosa was purified. The enzyme resembles another dipeptide hydrolase isolated from the cytosol fraction of intestinal mucosa. Studies on the binding of cytosol peptide hydrolase to brush-border membranes indicate that the enzyme found in the brush border may be a cytoplasmic contaminant.
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PMID:Similarities between a dipeptide hydrolase from brush-border and cytosol fractions of guinea-pig intestinal mucosa. 100 29

Brains from piglets were dissected and a block of tissue including the substantia nigra, globus pallidus, and entopeduncular nucleus was homogenized and then fractionated on discontinuous Percoll gradients. Ligand-binding assays using (-)-[3H]nicotine and [3H]quinuclidinyl benzilate served to delineate fractions containing nicotinic and muscarinic acetylcholine receptors. In this system endopeptidase-24.11 exhibited a biphasic distribution, consistent with its presence on both pre- and postsynaptic membranes. Peptidyl dipeptidase A (angiotensin converting enzyme; ACE) was associated with membrane fractions containing muscarinic receptors. An immunoblot of these fractions with an affinity-purified polyclonal antibody to ACE revealed only the neuronal form of ACE (Mr 170,000), the endothelial form (Mr 180,000) being undetectable. Electron microscopic immunoperoxidase staining of the substantia nigra, with an affinity-purified antibody to endopeptidase-24.11 at the preembedding stage, showed this antigen to be confined to the plasma membranes of boutons, axons, and some dendrites. Both pre- and postsynaptic membranes were stained, and occasionally other regions of the dendritic membrane were positive. No staining of synaptic vesicles within the boutons was observed. Thus, two independent approaches indicate that endopeptidase-24.11 is present on both pre- and postsynaptic membranes in the pig substantia nigra. The subcellular fractionation suggests that neuronal ACE is confined to dendritic membranes.
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PMID:Membrane localization of endopeptidase-24.11 and peptidyl dipeptidase A (angiotensin converting enzyme) in the pig brain: a study using subcellular fractionation and electron microscopic immunocytochemistry. 767 89

The expression of cell-surface peptidases was examined in two human colon carcinoma cell lines, Caco-2 and HT-29. Enzymic assays revealed the presence of eight cell-surface peptidases on a Caco-2 cell line (passage number 82-88), namely aminopeptidase N, dipeptidyl peptidase IV, peptidyl dipeptidase A (angiotension-converting enzyme), aminopeptidase P, aminopeptidase W, endopeptidase-24.11, gamma-glutamyl transpeptidase and membrane dipeptidase. The presence of dipeptidyl peptidase IV and endopeptidase-24.11 was also confirmed immunochemically. After 15 days culture, the activities of aminopeptidase P, peptidyl dipeptidase A and alkaline phosphatase activities on Caco-2 cells reached a plateau, and that of membrane dipeptidase began to decline. In contrast, aminopeptidase N, dipeptidyl peptidase IV and endopeptidase-24.11 activities were still rising after 26 days in culture. Caco-2 cells of passage number 181-183 were found to lack endopeptidase-24.11, but maintained dipeptidyl peptidase IV expression. Two populations of HT-29 cells were surveyed. Both the standard, undifferentiated population and a differentiated population expressed only three peptidases: dipeptidyl peptidase IV, aminopeptidase W and carboxypeptidase M. In the differentiated HT-29 cells the activity of dipeptidyl peptidase IV after 14-21 days was beginning to plateau whereas aminopeptidase W activity was still rising and that of carboxypeptidase M had begun to decline. These differences in activity profiles observed among this group of cell-surface peptidases indicate that these cell lines, especially Caco-2, are useful models to study the regulation of their expression.
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PMID:A survey of membrane peptidases in two human colonic cell lines, Caco-2 and HT-29. 131 37

The effects of a range of metallopeptidase inhibitors on the activities of the porcine kidney cell surface zinc aminopeptidases, aminopeptidase A (AP-A; EC 3.4.11.2), aminopeptidase N (AP-N; EC 3.4.11.7) and aminopeptidase W (AP-W; EC 3.4.11.16), have been directly compared. Amastatin and probestin were effective against all three aminopeptidases, with the concentration of inhibitor required to cause 50% inhibition (I50) in the low micromolar range (I50 = 1.5-20 microM), except for probestin with AP-N which displayed an I50 of 50 nM. Actinonin failed to inhibit significantly either AP-A or AP-W, and thus can be considered a relatively selective inhibitor (I50 = 2.0 microM) of AP-N. In contrast, bestatin was a relatively poor inhibitor of AP-N (I50 = 89 microM) and failed to inhibit AP-A, but was more potent towards AP-W (I50 = 7.9 microM). Thus, some of the observed chemotherapeutic actions of bestatin may be due to inhibition of cell-surface AP-W. A number of other metallopeptidase inhibitors, including inhibitors of endopeptidase-24.11 (EC 3.4.24.11) and membrane dipeptidase (EC 3.4.13.11), and the carboxylalkyl and phosphoryl inhibitors of angiotensin converting enzyme (EC 3.4.15.1) failed to inhibit significantly AP-A, AP-N or AP-W. However, AP-W was inhibited with I50 values in the micromolar range by the sulphydryl converting enzyme inhibitors rentiapril (I50 = 1.6 microM), zofenoprilat (I50 = 7.0 microM) and YS 980 (I50 = 17.7 microM). Neither AP-A nor AP-N were affected by these sulphydryl compounds. Inhibition of AP-W may account for some of the side effects noted with the clinical use of the sulphydryl converting enzyme inhibitors. The availability of compounds which are totally selective for AP-W over any of the other mammalian cell surface zinc aminopeptidases may aid in identifying endogenous substrates, and thus physiological or pathophysiological role(s) of AP-W.
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PMID:Inhibition of aminopeptidases N, A and W. A re-evaluation of the actions of bestatin and inhibitors of angiotensin converting enzyme. 136 Feb 11


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