Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.24.11 (CD10)
9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aminopeptidase activities were identified in extracts of kidney, ovotestis, head ganglia, heart and haemolymph of Aplysia californica. These enzyme preparations hydrolysed [3H][Leu]enkephalin at the Try-1-Gly-2 bond as determined by h.p.l.c. analysis of cleavage products. In all these tissues, enkephalin-degrading aminopeptidase activities were present both in membrane-bound and cytosolic fractions. The bivalent-cation-chelating agent, 1,10-phenanthroline, inhibited kidney membrane aminopeptidase activity with an IC50 of 30 microM, suggesting that this enzyme is a metalloproteinase. The aminopeptidase inhibitor amastatin was the most potent inhibitor of [Leu]enkephalin degradation (IC50 25 nM) by membrane-bound aminopeptidase, and bacitracin, bestatin and puromycin were about 100-1000 times less potent. In contrast with membrane-bound aminopeptidase, the cytosolic form is sensitive to puromycin. Angiotensin-converting enzyme inhibitor had no effect on [Leu]enkephalin degradation by kidney membranes, while the neutral endopeptidase inhibitors were poor inhibitors of the enzymes in this preparation. The Km values of the aminopeptidase in the kidney membranes and cytosolic fractions for the [Leu]enkephalin substrate were 2.4 and 7.4 microM respectively. The aminopeptidase present in the kidney membranes also hydrolysed endogenous Phe-Met-Arg-Phe-amide peptide at the Phe-1-Met-2 bond as well as synthetic alanine p-nitroanilide and leucine p-nitroanilide. When used in a competition assay, these substrates inhibited hydrolysis of [3H][Leu]enkephalin, suggesting that the same enzyme degraded all these substrates. Taken together, these results suggest that Aplysia tissues contain both a membrane-bound aminopeptidase related to the mammalian aminopeptidase N and a cytosolic puromycin-sensitive aminopeptidase.
...
PMID:Identification and characterization of aminopeptidases from Aplysia californica. 141 57

The s.c. administration of [Met5]-enkephalin to 10-day-old rats pretreated with the mixture of 3 peptidase inhibitors, amastatin, captopril and phosphoramidon, produced the inhibition of tail-flick response and loss of righting reflex. When infant rats were pretreated with the mixture of any combination of two peptidase inhibitors, however, the change in both the response and the reflex were not produced at all by enkephalin injection, indicating that 3 kinds of enzymes, amastatin-sensitive aminopeptidase(s), captopril-sensitive peptidyl dipeptidase A and phosphoramidon-sensitive endopeptidase 24.11, played an important role in the inactivation of enkephalin after its systemic administration. Additionally, the fact that the two enkephalin-induced effects were more effectively antagonized by naloxone, a relatively selective mu-opioid antagonist, than by naltrindole, a specific delta-antagonist, or by nor-binaltorphimine, a specific kappa-antagonist, showed that these two effects were produced by the interaction of enkephalin with mu receptors. Moreover the involvement of mu receptors in the production of these two effects was shown by the fact that the s.c. administration of [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a selective mu agonist, also produced these two effects which were more effectively antagonized by naloxone than by naltrindole or nor-binaltorphimine. Since the magnitude of the two effects induced by enkephalins in 15-day-old rats was significantly lower than that in 10-day-old rats, and the two enkephalin-induced effects were not produced at all in 20-day-old rats, a maturation-induced decrease in the permeability of the blood-brain barrier against opioid peptides was indicated.
...
PMID:Effects of the subcutaneous administration of enkephalins on tail-flick response and righting reflex of developing rats. 142 2

The effects of the endopeptidase 24.11 ('enkephalinase') inhibitor thiorphan, the aminopeptidase inhibitor bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the K(+)-evoked release of immunoreactive neurotensin and neuromedin N (iNT and iNN) from mouse hypothalamic slices were examined. (JMV 390-1 inhibits several metallopeptidases including endopeptidases 24.11, 24.15 and 24.16, and aminopeptidase N equipotently with Ki values around 50 nM.) Thiorphan increased the recovery of released iNT nearly 2-fold and had no effect on iNN. Bestatin produced a 4-fold increase in iNN recovery and was inactive on iNT. Finally, iNT and iNN recoveries were increased up to 4- and 5-fold, respectively, by JMV 390-1. These results show that in the mouse hypothalamus endopeptidase 24.11 participates with other metalloendopeptidases to the degradation of endogenously released NT while endogenously released NN is principally degraded by aminopeptidase(s).
...
PMID:Effects of thiorphan, bestatin and a novel metallopeptidase inhibitor JMV 390-1 on the recovery of neurotensin and neuromedin N released from mouse hypothalamus. 145 16

Employing soluble denatured protein substrates and their derivatives, the proteolytic activity of rat cathepsin H was investigated. The enzyme showed aminopeptidase activity which sequentially released amino acid from the N-terminal of the substrate. The aminopeptidase activity did not act on N alpha-acetylated peptides and showed moderate ionic-strength dependence when methionyl-methylcoumarylamide was employed as a substrate. These results indicate that the activity essentially requires an N-terminal free amino group of the substrate and recognizes it electrostatically to some extent. On the other hand, the enzyme was also indicated to exhibit endopeptidase activity by employing appropriate N alpha-acetylated peptide substrates. In contrast to the aminopeptidase activity, the endopeptidase activity showed rather strict specificity, preferring hydrophobic residues at P2 and P3 sites. Because of the broad specificity and high efficiency of the aminopeptidase activity, it was difficult to directly observe endopeptidase activity in the digestion of large peptide substrates with a free alpha-amino terminal. Thus, this is the first experimental evidence that indicates endopeptidase activity by assigning internal peptide bonds cleaved by this activity. From this data, we proposed a model of the binding site of this enzyme.
...
PMID:Endo- and aminopeptidase activities of rat cathepsin H. 152 52

After i.v. injection of 125I-labeled rat atrial natriuretic factor ([125I] ANF; 99-126) in tracer dose to mice, a saturable binding to lung membranes was evidenced using a filtration assay. Analysis of the membrane-bound radioactivity by high-pressure liquid chromatography indicated that it corresponded to the intact hormone in sinorphan-treated mice. [125I]rANF binding was inhibited completely by i.v. administration of rANF with an ED50 of 1.0 +/- 0.1 nmol/kg, a value obtained in sinorphan-treated mice. SC 416,542, an ANF analog with a four amino acid deletion in its ring, representing a selective ligand of ANF clearance receptors, was as potent as rANF in inhibiting the in vivo binding. By contrast, ANF fragments produced by enkephalinase (EC 3.4-24.11, membrane metalloendopeptidase) were less potent or even inactive in competing with [125I]rANF. It is concluded that [125I]rANF binding to lung membranes in vivo occurs to clearance receptors. [125I]rANF binding was enhanced by more than 2-fold in mice receiving enkephalinase inhibitors such as sinorphan and, although to a lesser extent, aminopeptidase inhibitors; on the other hand inhibitors of a variety of other peptidases were ineffective. These data confirm by a novel approach that enkephalinase plays a key role in the inactivation of circulating ANF. Hence, the in vivo binding test can be used to assess the activity of clearance receptor ligands and peptidase inhibitors, two classes of drugs affecting ANF metabolism, with potential clinical utility in cardiovascular and salt-retaining diseases.
...
PMID:Binding of [125I]atrial natriuretic factor to mouse lung membranes in vivo: characterization and effects of peptidase inhibitors. 153 34

The metacestode of Taenia solium persists for years in the human central nervous system. As proteolytic enzymes play an important role in the survival of tissues helminths, we examined extracts of T. solium metacestodes for proteolytic activity using 9 synthetic peptide substrates and 3 proteins (hemoglobin, albumin, and immunoglobulin G). The proteolytic enzymes were classified based on their inhibitor profiles. At neutral pH, aminopeptidase(arginine-7-amino-4-trifluoromethylcoumarin) and endopeptidase(benzyloxy-carbonyl-glycine-glycine-arginine-7-amino-4- trifluoromethylcoumarin) substrates were cleaved. Hydrolysis of both substrates was inhibited by chelating agents, which inhibit metalloproteases. Peak activity with both substrates eluted in gel filtration fractions corresponding to a molecular weight of about 104 kDa. Cysteine protease activity was identified, which cleaved benzyloxy-carbonyl-phenylalanine-arginine-7-amino- 4-trifluoromethylcoumarin (Z-Phe-Arg-AFC) and hemoglobin. Cleavage of Z-Phe-Arg-AFC was maximal at acid pH, was stimulated by thiols, and was inhibited by leupeptin and Ep459. Peak cysteine protease activity eluted in gel filtration fractions corresponding to a molecular weight of 32 kDa. Aspartic protease activity was identified by specific inhibition with pepstatin of acid digestion of hemoglobin and immunoglobulin G. Immunoglobulin digestion occurred at acid pH, with preferential degradation of the heavy chain. Upon gel filtration chromatography, the aspartic protease activity eluted as a broad peak with maximal activity at about 90 kDa. No serine protease activity was detected. None of the parasite enzymes digested albumin. Proteolytic enzymes of T. solium may be important for parasite survival in the intermediate host, by providing nutrients and digesting host immune molecules.
...
PMID:Detection and preliminary characterization of Taenia solium metacestode proteases. 155 44

An intracellular aminopeptidase from Streptococcus salivarius subsp. thermophilus strain ACA-DC 114, isolated from traditional Greek yoghurt, was purified by chromatography on DEAE-cellulose and Sephadex G-100. The enzyme had a molecular weight of 89,000. It was active over a pH range 4.5-9.5 and had optimum activity on L-lysyl-4-nitroanilide at pH 6.5 and 35 degrees C with Km = 1.80 mmol/l; above 55 degrees C the enzyme activity declined rapidly. The aminopeptidase was capable of degrading substrates by hydrolysis of the N-terminal amino acid; it had very low endopeptidase and no carboxypeptidase activity. The enzyme was strongly inactivated by EDTA. Serine and sulphydryl group reagents had no effect on enzyme activity.
...
PMID:Purification and partial characterization of an intracellular aminopeptidase from Streptococcus salivarius subsp. thermophilus strain ACA-DC 114. 156 49

1. The depolarizing responses to angiotensin II and angiotensin III of the rat superior cervical ganglion have been characterized in vitro, by the use of peptidase inhibitors, peptide and non-peptide antagonists and dithiothreitol (DTT). 2. Angiotensin II and III depolarized the ganglion in a concentration-related manner. Angiotensin II was approximately 30 fold more potent than angiotensin III. 3. The endopeptidase inhibitor, bacitracin, increased the potency of angiotensin II and III by approximately 4 and 20 fold respectively. The aminopeptidase inhibitor, amastatin, further increased the potency of angiotensin III (but not angiotensin II) by approximately 4 fold. In the presence of bacitracin and amastatin, angiotensin II and III were equipotent. 4. The peptide antagonist [Ile7]angiotensin III (0.01-0.3 microM) produced a non-parallel rightward displacement of the angiotensin II concentration-response curve, with a suppression of the maximum response. The potency of [Ile7]angiotensin III was increased by bacitracin and amastatin. 5. The AT1-selective non-peptide antagonist losartan (DuP 753; 0.03 and 0.1 microM) produced a parallel rightward displacement of the angiotensin II concentration-response curve, with an apparent pKB of 8.3 +/- 0.1. A higher concentration of losartan (0.3 microM) depressed the maximum agonist response by 32 +/- 6.5%, possibly reflecting non-competitive behaviour of the antagonist. The potency of losartan was not influenced by bacitracin. 6. The AT2-selective non-peptide antagonist, PD123177 (3 microM) failed to antagonize the angiotensin II-induced depolarizations. 7. DTT (1 mM) produced a 22% reduction of the maximum response to angiotensin II.8. We conclude that the angiotensin II-induced depolarizations of the rat superior cervical ganglion are mediated by angiotensin II receptors of the AT1 subclass. The ability of peptidase inhibitors to modify the potency of peptide agonists and antagonists highlights the difficulties associated with the use of peptide agents to characterize angiotensin II receptors in this preparation.
...
PMID:Pharmacological characterization of angiotensin-induced depolarizations of rat superior cervical ganglion in vitro. 162 55

In addition to angiotensin I converting enzyme (ACE; EC 3.4.15.1) and carboxypeptidase N (CPN; EC 3.4.17.3), other peptidases contribute to bradykinin (BK) degradation in plasma. Rat plasma degraded BK by hydrolysis of the N-terminal Arg1-Pro2 bond, and the characteristics of hydrolysis are consistent with identification of aminopeptidase P (APP; EC 3.4.11.9) as the responsible enzyme. BK and BK[1-5] N-terminal hydrolysis was optimal at neutral pH, was inhibited by 2-mercaptoethanol, dithiothreitol, o-phenanthroline and EDTA, but was unaffected by the aminopeptidase inhibitors amastatin, puromycin and diprotin A, the endopeptidase-24.11 inhibitors phosphoramidon and ZINCOV, and the ACE and CPN inhibitors captopril and D,L-mercapto-methyl-3-guanidinoethylthiopropanoic acid (MERGETPA), respectively. Although kallidin (Lys-BK) was not metabolized directly by APP, conversion to BK by plasma aminopeptidase M (EC 3.4.11.2) resulted in subsequent degradation by APP. BK analogs containing N-terminal Arg1-Pro2 bonds, including [Tyr8-(OMe)] BK and [Phe8 psi(CH2NH)Arg9]BK (B2 agonists), des-Arg9-BK and [D-Phe8]des-Arg9-BK (B1 agonists), and [Leu8]des-Arg9-BK (B1 antagonist), were degraded by APP with Km and Vmax values comparable to those found for BK (Km = 19.7 +/- 2.6 microM; Vmax = 12.1 +/- 1.2 nmol/min/mL). In contrast, B2 antagonists containing D-Arg0 N-termini, including D-Arg[Hyp3,Thi5.8,D-Phe7]BK and D-Arg[Hyp3,D-Phe7,Phe8 psi(CH2NH)Arg9]BK, were resistant to APP-mediated hydrolysis. These data support a role for plasma aminopeptidase P in the degradation of circulating kinins, and a variety of B2 and B1 kinin agonists and antagonists. However, APP does not participate in the degradation of D-Arg0-containing antagonists.
...
PMID:Metabolism of bradykinin agonists and antagonists by plasma aminopeptidase P. 165 Oct 78

We examined the effect of rapid intravenous infusion of neurokinin A (NKA) and selected COOH-terminal NKA fragments on pulmonary conductance (GL) and dynamic compliance in anesthetized mechanically ventilated guinea pigs. The rank order of the dose of peptide required to reduce GL by 50% (ED50GL) was NKA = NKA2-10 = NKA3-10 = NKA4-10 less than NKA5-10 much less than NKA6-10. The time course of bronchoconstriction induced by NKA2-10, NKA3-10, and NKA4-10 was similar to that induced by NKA, whereas NKA5-10 and NKA6-10 each had a shorter duration of action than NKA for a similar induced maximal change in GL. To determine whether degradation of these NKA fragments by neutral endopeptidase (NEP) modulates their bronchoconstrictor activity as it does for native NKA, we examined the effect of the NEP inhibitor SCH32615 on NKA3-10-, NKA5-10-, and NKA6-10-induced changes in GL. We have previously reported that the ED50GL for NKA was approximately 20-fold lower in animals pretreated with SCH32615 (1 mg/kg) than in control guinea pigs. SCH32615 caused a 16-fold decrease in ED50GL for NKA3-10 (P less than 0.001) but had no effect on airway responses to NKA5-10 or NKA6-10. The results demonstrate that the magnitude and duration of bronchoconstriction induced by potential aminopeptidase degradation products of NKA are similar to those of the native peptide. Aminopeptidases do not, therefore, have the capacity to modulate the bronchoconstriction induced by this peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Relative bronchoconstrictor activity of neurokinin A and neurokinin A fragments in guinea pigs. 165 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---