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

Regional differences in neurotensin metabolism and the peptidases involved were studied using intact, viable rat brain microslices and specific peptidase inhibitors. Regional brain slices (2 mm x 230 microns) prepared from nucleus accumbens, caudate-putamen, and hippocampus were incubated for 2 h in the absence and presence of phosphoramidon, captopril, N-[1(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate, and o-Phenanthroline, which are inhibitors of neutral endopeptidase 24.11, angiotensin-converting enzyme, metalloendopeptidase 24.15, and nonspecific metallopeptidases, respectively. Neurotensin-degrading proteolytic activity varied by brain region. Significantly less (35.0 +/- 1.6%) neurotensin was lost from hippocampus than from caudate-putamen (45.4 +/- 1.0%) or nucleus accumbens (47.8 +/- 1.1%) in the absence of inhibitors. Peptidases responsible for neurotensin metabolism on brain slices were found to be predominantly metallopeptidases. Metalloendopeptidase 24.15 is of major importance in neurotensin metabolism in each brain region studied. The relative contribution of specific peptidases to neurotensin metabolism also varied by brain region; angiotensin-converting enzyme and neutral endopeptidase 24.11 activities were markedly elevated in the caudate-putamen as compared with the nucleus accumbens or hippocampus. Interregional variation in the activity of specific peptidases leads to altered neurotensin fragment formation. The brain microslice technique makes feasible regional peptide metabolism studies in the CNS, which are impractical with synaptosomes, and provides evidence for regional specificity of neurotensin degradation.
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PMID:Specificity of neurotensin metabolism by regional rat brain slices. 172 5

The simple determination of the Neutral Metalloendopeptidase (NEP, Enkephalinase A) with the known fluorogenic substrate Dansyl-D-Ala-Gly-(pNO2)Phe-Gly is disturbed by high concentrations of the Angiotensin-Converting-Enzyme (ACE). ACE hydrolyzes this substrate too but to a smaller degree. In some tissues and body fluids a further substrate hydrolysis takes place by any indefinite proteases. Finally the enzymatic hydrolysis of the NEP-substrate is inhibited by phosphate ions. A method is proposed for the elimination of this disturbances in the NEP-determination with a phosphate-free buffer using two comparison tests with Lisinopril and o-Phenanthroline. The resulting NEP-activity is calculated very simple thereafter.
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PMID:[The determination of neutral metalloendopeptidase (enkephalinase A) in biological material]. 285 71

In order to identify which peptidases are involved in the catabolism of neurotensin in the CNS, [3H-Tyr3,11]-neurotensin was superfused over rat hypothalamic slices in the presence and absence of peptidase inhibitors. The degree of degradation of the peptide was determined by reverse phase HPLC separation of 3H-labelled neurotensin from 3H-labelled products. Very little degrading activity was released from the slice into the medium during the superfusion. In the absence of inhibitors, 20 to 50% of 3H-neurotensin was degraded giving mainly 3H-Tyr along with other unidentified 3H-labelled products. Inhibitors of endopeptidase 24.11 (phosphoramidon) and proline endopeptidase (antibody) had no effect on the degradation. Captopril, an inhibitor of angiotensin converting enzyme, had a small inhibitory effect. In contrast, dynorphin(1-13), an inhibitor of a soluble, thiol dependent metallopeptidase which hydrolyses neurotensin at Arg8-Arg9, gave greater than 80% inhibition of 3H-neurotensin degradation in the slice preparation. 1,10-Phenanthroline, an inhibitor of metallopeptidases, was also an effective inhibitor. The dynorphin sequence responsible for the inhibition contains the Arg6-Arg7 bond. Other peptides (bradykinin and angiotensin) which are substrates of the soluble metallopeptidase also inhibited neurotensin breakdown by the slice. This evidence suggests that this thiol dependent metalloendopeptidase is the major neurotensin catabolizing enzyme in hypothalamic slices.
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PMID:Peptidases involved in the catabolism of neurotensin: inhibitor studies using superfused rat hypothalamic slices. 352 99

1. The degradation of bradykinin (BK) labelled with tritiated proline at positions 2 and 3 ([3H]-BK) was determined on the luminal surface of bovine tracheal epithelium, in supernatants obtained from incubations of the luminal tracheal surface, and in suspensions of isolated tracheal epithelial cells. Peptidase inhibitors and identification of peptide fragments were used for characterization of the metabolic pathways. 2. On the luminal surface of intact bovine trachea, [3H]-BK was degraded with a half life of 12.8 min. [1-7]-BK and [1-5]-BK were the major direct metabolites which were further degraded via [1-3]-BK and [2-3]-BK to proline. Metabolism of [3H]-BK was unaltered in the presence of ramiprilat (250 nM) or phosphoramidon (10 microM). Phenanthroline diminished the formation of [1-7]- and [1-5]-BK and abolished the generation of proline. 3. Supernatants obtained from incubations of tracheal epithelium contained kininase activities which steadily increased when tracheae were incubated for longer than 30 min. After 60 min contact with epithelium, the incubation medium contained higher kininase activities than the epithelium itself. The spectrum of kinin metabolites generated by kininases in the supernatant was comparable to that formed by intact epithelium. 4. In suspensions of isolated epithelial cells, [3H]-BK was degraded with a half life of 70 min. The metabolites [1-3]- and [2-3]-BK were formed in parallel to [1-7]- and [1-5]-BK; however, proline was not generated. Degradation of [3H]-BK was not influenced by ramiprilat, but was inhibited by 85% in the presence of phosphoramidon. Phosporamidon markedly inhibited the generation of [1-7]- and [1-5]-BK and nearly abolished the formation of [1-3]- and [2-3]-BK. 5. In conclusion, angiotensin I-converting enzyme and neutral endopeptidase 24.11 are not significantly involved in [3H]-BK degradation on the luminal side of intact tracheal epithelium. The spectrum of metabolites found may in fact reflect the combined activities of metalloendopeptidase 24.15 and post-proline cleaving enzymes. Enzymes showing similar kininase activities are also released from the epithelium. Isolated epithelial cells contain low activities of these kininases, but a high activity of neutral endopeptidases, which may reflect an exclusively basolateral localization of the latter.
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PMID:Degradation of bradykinin by bovine tracheal epithelium and isolated epithelial cells. 911 86