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)

1. Bradykinin (BK) instilled directly into the airway lumen caused bronchoconstriction in anaesthetized, mechanically ventilated guinea-pigs in the presence of propranolol (1 mg kg-1 i.v.). The geometric mean dose of BK required to produce 100% increase in airway opening pressure (PD100) was 22.9 nmol (95% c.i. 11.7-44.6 nmol). 2. The dose-response curve for the effect of instilled BK was significantly shifted to the left by the angiotensin converting enzyme (ACE) inhibitor, captopril (5 and 50 nmol instillation, PD100 = 3.0, 95% c.i. 0.98-8.9, and 2.0 nmol, 95% c.i. 0.65-6.2 nmol, respectively). 3. The neutral endopeptidase (NEP) inhibitor, phosphoramidon (5 and 50 nmol instillation) also shifted the dose-response curve for the effect of instilled BK; the PD100 values = 2.2 (95% c.i. 0.40-11.7) and 1.8 nmol (95% c.i. 0.87-3.5 nmol), respectively. 4. After pretreatment with captopril (50 nmol) and phosphoramidon (50 nmol) in combination, the dose-response curve for the effect of instilled BK (PD100 = 1.1 nmol, 95% c.i. 0.37-3.2 nmol) was similar to that obtained in the presence of each inhibitor used alone. 5. The kinase I inhibitor, DL-2-mercaptomethyl-3-guanidinoethylthiopropionic acid (50 nmol instillation) failed to alter the dose-response curve to instilled BK (PD100 = 14.6 nmol, 95% c.i. 6.7-32.0 nmol). 6. These data suggest that both ACE and NEP degrade BK in the airway lumen, but that kininase I is not involved.
Br J Pharmacol 1990 Sep
PMID:The effect of peptidase inhibitors on bradykinin-induced bronchoconstriction in guinea-pigs in vivo. 228 70

Recently, it has been hypothesized that the N-terminal portion of substance P (SP), SP(1-7), which results from the action of endopeptidase 24.11 (EC3.4.24.11), could be involved in mediating the depressor effects of baroreceptor afferent activation via its action on cells in the nucleus tractus solitarius (NTS). In this study, the binding of a monoclonal antibody to endopeptidase 24.11 was examined immunohistochemically at the level of the caudal medulla of the rat brain. By light microscopy, intense immunoreactivity was seen in the NTS, in fibers bordering the area postrema, and in the area postrema itself. After electron microscopy, endopeptidase 24.11-like immunoreactivity was seen to be associated with the cytoskeleton and plasma membrane in axons, dendrites and glial processes. Antigen was also associated with synaptic vesicles and plasma membranes in presynaptic terminals forming mainly axo-dendritic synapses typical of vagal afferent terminals involved in the baroreceptor reflex. Thus, endopeptidase 24.11 appears to be localized at sites where it could effectively process SP prior to its binding to postsynaptic receptors.
Neurosci Lett 1990 Sep 04
PMID:Immunocytochemical localization of endopeptidase-24.11 in the nucleus tractus solitarius of the rat brain. 229 Jun 20

In this study, we applied mAb and heterologous antisera in double marker combinations to investigate the phenotype and the proliferative activity of immature B lineage cells in XLA. Bone marrow (BM) samples from eight male adult patients with no circulating B lymphocytes were studied. The proportions and the phenotype of the earliest identifiable B cell progenitors, expressing nuclear terminal deoxynucleotidyl transferase (TdT), cytoplasmic CD22, and membrane CD19 and CD10 were identical to those observed in normal BM. In XLA these cells represented 1.2% to 22% of BM mononuclear cells; 5% to 42% and 1% to 45% of such cells weakly expressed CD20 and CD37, respectively, and invariably lacked CD13 and CD33. Cytoplasmic mu+ sIg- pre-B cells were seen in low numbers (0.1% to 0.3%) in four samples and were undetectable in the remaining four. Consequently, the ratio TdT+/c mu+ was greater than 100 in five out of eight samples studied in contrast to the less than 10 values seen in normal individuals. The proliferative activity of B lineage progenitor cells was studied by using Ki67 and anti-bromodeoxyuridine mAb. Although the proliferation of TdT+ cells in XLA was comparable with that seen in normal BM samples (24% to 59% of TdT+ were Ki67+ and 11% to 27% incorporated bromodeoxyuridine), this was dramatically reduced in the c mu+ cells (no c mu+, Ki67+ seen in three samples where pre-B cells were observed). Thus, the abnormalities of B cell differentiation in XLA are first seen at the c mu+ pre-B stage and suggest a maturation block in the transition between TdT+, c mu- pre-pre-B cells and c mu+ pre-B cells. The severity of this block may be variable, allowing the generation of a near normal number of pre-B cells in some patients, which nevertheless have a defective proliferative activity. Finally, our study further supports the concept that the effects of the "XLA gene" are confined within the B lineage by demonstrating that the proportions of T cells bearing TCR-alpha beta and TCR-gamma delta in XLA are similar to those seen in normal individuals.
J Immunol 1990 Sep 15
PMID:Phenotypic features and proliferative activity of B cell progenitors in X-linked agammaglobulinemia. 239 16

Reversible synthetic inhibitors are characterized for Astacus protease, a 22,614-Da zinc containing neutral endopeptidase from the digestive tract of crayfish. Effective inhibition was demonstrated for several simple thiol containing compounds and a series of amino acid hydroxamates. Both classes of inhibitors had ID50 values ranging from 10(-2) to 10(-4) M for inhibition of hydrolysis of succinyl-Ala-Ala-Ala-p-nitroanilide. Tyrosine hydroxamate was found to be the most effective inhibitor with an ID50 of 175 microM and the mode of inhibition by this compound was determined to be of the simple noncompetitive type. In contrast to the other inhibitors tested, cysteine was seen to partially inactivate the enzyme in a time-dependent manner. The kinetics of this process was studied in detail using progress curve analysis. It was determined that cysteine was acting as a weak chelator and slowly establishing an equilibrium between metallo- and apoenzyme. In the presence of the strong zinc scavenger EDTA, cysteine can, in effect, function as a catalyst in transferring the metal from the protein to the secondary chelator at a rate 10,000 times faster than the rate of unassisted zinc dissociation. The series of amino acid hydroxamates served as probes into the microenvironment of the active site. Possible binding modes of the inhibitors are discussed on the basis of the relationship between the chemical nature of the inhibitor side chains and the strength of inhibition.
Arch Biochem Biophys 1990 Sep
PMID:Thiol containing compounds and amino acid hydroxamates as reversible synthetic inhibitors of Astacus protease. 239 1

Carboxypeptidase M, a plasma membrane-bound enzyme, is present in many human organs and differs from other carboxypeptidase that cleave basic COOH-terminal amino acids. Cultured Madin-Darby canine kidney (MDCK) distal tubular cells contain a kininase I-type enzyme that inactivates bradykinin by releasing Arg9. We found the properties of this kininase to be identical with carboxypeptidase M. In fractionated cells, carboxypeptidase activity sediments with membranes; and detergents, trypsin, and phosphatidylinositol-specific phospholipase C solubilize it, similar to results with human placental carboxypeptidase M. Ten microM 2-mercaptomethyl-3-guanidinoethylthiopropanoic acid and 1 mM o-phenanthroline inhibit, whereas 1.0 mM CoCl2 activates the enzyme. It has a neutral pH optimum and cleaves COOH-terminal Arg or Lys in bradykinin and in shorter peptides. The relative hydrolysis rates of peptides in the presence or absence of 1 mM CoCl2 were similar to those obtained with human carboxypeptidase M. The carboxypeptidase in MDCK cells (54 kDa) cross-reacts with antibodies to human carboxypeptidase M in Western blotting, but not with antibodies to plasma carboxypeptidase N. The enzyme is a glycoprotein; chemical deglycosylation reduced the size to 48 kDa. The presence of the enzyme on the cell membrane of MDCK cells was also shown with transmission electron microscopy using immunogold, which indicated that the enzyme is on the apical side. In addition, MDCK cells contain neutral endopeptidase 24.11 (enkephalinase) and prolylcarboxypeptidase (angiotensinase C) activities. Partitioning of solubilized carboxypeptidase M into Triton X-114 and water indicates that trypsin and phospholipase C remove a hydrophobic tail, while detergent solubilization leaves the hydrophobic moiety intact. Labeling of MDCK cells with [3H]ethanolamine resulted in the synthesis of radiolabeled carboxypeptidase M as determined by immunoprecipitation and fluorography. Thus, MDCK cells contain membrane-bound carboxypeptidase M, which is anchored to the plasma membrane via phosphatidylinositol-glycan. As a major kininase of the distal tubules, it may regulate salt and water excretion.
J Biol Chem 1990 Sep 05
PMID:Carboxypeptidase M in Madin-Darby canine kidney cells. Evidence that carboxypeptidase M has a phosphatidylinositol glycan anchor. 239 13

Nonadrenergic, noncholinergic contractile responses of guinea pig hilar bronchi to transmural electrical stimulation (TES) have been suggested to be due to release of endogenous tachykinins from capsaicin-sensitive neurons (C-fibers). Thiorphan and phosphoramidon, inhibitors of neutral endopeptidase (NEP, the major enzyme responsible for degrading tachykinins), were found to potentiate contractile responses of this isolated airway segment to TES and exogenously applied capsaicin, substance P and neurokinin A. However, the magnitude of potentiation by either inhibitor was smaller for TES and capsaicin (less than 10-fold leftward shift) than for the substrate agonists (about 100-fold leftward shift). This quantitative difference in potentiation by NEP inhibitors does not appear to be due to an influence of vasoactive intestinal peptide or calcitonin gene-related peptide, two endogenous peptides that might be released concomitantly by TES. Neither peptide caused marked effects on contractile responses to TES or tachykinins when applied to the isolated tissues. Addition of inhibitors of serine proteases, aminopeptidases, acetylcholinesterase and angiotensin-converting enzyme failed to further potentiate responses to TES in the presence of thiorphan. Therefore, the contractile response does not appear to be further modified by the activity of these peptidases. Neuropeptide gamma, but not neuropeptide K, was potentiated by thiorphan. The data suggest that peptides that are not substrates for NEP (for example, neuropeptide K) may also be released by TES from capsaicin-sensitive neurons to cause contraction. This may, at least in part, explain the quantitative difference in potentiation by NEP inhibitors of contractile responses to TES and to exogenously applied NEP-sensitive tachykinins in the guinea pig hilar bronchus.
J Pharmacol Exp Ther 1990 Sep
PMID:Pharmacologic studies on the differential influence of inhibitors of neutral endopeptidase on nonadrenergic, noncholinergic contractile responses of the guinea pig isolated hilar bronchus to transmural electrical stimulation and exogenously applied tachykinins. 239 13

During the diagnostic investigation of 750 acute leukemias, nine cases were morphologically, cytochemically, and phenotypically undifferentiated. In seven of these cases the blasts were class II+, CD34+ and TdT+, in one were class II+, TdT+, CD7+ while in the remaining leukemia blasts expressed class II only. Cytoplasmic and membrane CD22, CD3, CD13, and Ig as well as membrane CD19, CD10, CD37, CD2, CD33, CD14, glycophorin C, and CD61 were absent. The further characterization of these rare leukemias yielded the following results. The TCR-beta, -gamma and -delta genes were in germline configuration in seven cases studied while IgH genes were rearranged on both alleles in two cases and germline in the other five. By ultrastructural analysis peroxidase activity was detected on unfixed cells in a minority of blasts from four of seven cases. In two of the peroxidase-positive cases a small proportion of blasts also reacted with an anti-myeloperoxidase monoclonal antibody. In one of the peroxidase-negative cases, 7% of blasts were labeled by the antibody, suggesting the presence of peroxidase in its proenzyme form. Importantly, the two cases with Ig gene rearrangements did not have cytochemically or immunologically detectable peroxidase. Three of the nine patients were treated as ALL while six received AML chemotherapy. In five patients complete remission was achieved while the other four died from infections during remission induction. Four patients are still in remission 7, 12, 24, and 30 months after diagnosis while one patient relapsed after 12 months. In conclusion, we have characterized the genotypic and ultrastructural features of subtype of acute leukemia in which blasts expressed immaturity markers and lacked lineage associated antigens. In contrast to previously reported "unclassifiable" cases, the leukemias were phenotypically homogeneous and showed a good response to chemotherapy.
Leukemia 1990 Sep
PMID:Phenotypic, genotypic, cytochemical, and ultrastructural characterization of acute undifferentiated leukemia. 239 82

Calcitonin gene-related peptide (CGRP) was found to potently inhibit a substance P endopeptidase isolated from human CSF. CGRP potentiated substance P irritant actions; a possible mechanism is interaction for a common metabolic step. Somatostatin is another peptide capable of competing with substance P endopeptidase.
Eur J Pharmacol 1985 Sep 24
PMID:Calcitonin gene-related peptide is a potent inhibitor of substance P degradation. 241 71

Membrane vesicles, showing a 21 +/- 2-fold enrichment in the activity of 5'-nucleotidase and a 11 +/- 4-fold enrichment in the activity of angiotensin-converting enzyme relative to homogenate, were prepared from the myenteric plexus-containing longitudinal muscle layer of guinea pig ileum. Incubation of the vesicles with substance P and neurokinin A led to degradation of the peptides, and metabolites were isolated by reverse-phase HPLC and identified by amino acid composition. Cleavages of substance P between Glu6-Phe7, Phe7-Phe8, and Gly9-Leu10 and of neurokinin A between Gly8-Leu9 were observed and could be inhibited in a dose-dependent manner by phosphoramidon, an inhibitor of neutral endopeptidase 24.11. Formation of these metabolites was not completely inhibited by this agent, indicating that a phosphoramidon-insensitive form of endopeptidase 24.11 was present in the gut. Substance P was resistant to degradation by aminopeptidases, but neurokinin A was a substrate for bestatin-sensitive aminopeptidase(s), so that the neurokinin A (3-10) fragment represented the predominant metabolite in the chromatograms. The rate of formation of all the metabolites was not inhibited by enalapril and not enhanced by an increased Cl- concentration, indicating that angiotensin-converting enzyme was unimportant in the degradation process. Degradation of neurokinin A by the vesicles (Km 30 microM; Vmax 7.2 +/- 0.8 nmol min-1 mg of protein-1) was more rapid than degradation of substance P (Km 25 microM; Vmax 4.4 +/- 0.4 nmol min-1 mg of protein-1).
J Neurochem 1986 Sep
PMID:Proteolytic inactivation of substance P and neurokinin A in the longitudinal muscle layer of guinea pig small intestine. 242 10

The primary structure of a 9-kDa basic protein from rice seeds was determined by gas-phase sequencing of the intact protein and peptides derived from it by digestion with trypsin, chymotrypsin, and endopeptidase Lys-K. The protein consists of a single polypeptide chain of 91 amino acid residues with a calculated molecular mass of 8909 Da. It is rich in alanine, serine, glycine, and cysteine. The eight cysteines form four disulfide bonds. There is no methionine, histidine, phenylalanine, or tryptophan. The sequence is highly homologous with an alpha-amylase inhibitor, I-2, from seeds of Indian finger millet [F. A. P. Campos and M. Richardson (1984) FEBS Lett. 167, 221-225] and a 10-kDa barley seed protein, also called a probable amylase/protease inhibitor [B. Svensson et al. (1986) Carlsberg Res. Commun. 51, 493-500; J. Mundy and J. C. Rogers (1986) Planta 169, 51-63]. In analogy with the barley protein, the purified protein is tentatively called a rice probable amylase/protease inhibitor (PAPI). The rice PAPI does not show inhibitory activities against proteases and amylases tested. The amino acid sequence is as follows: Ile-Thr-Cys-Gly-Gln-Val-Asn-Ser-Ala-Val(10)-Gly-Pro-Cys-Leu-Thr-Tyr- Ala-Arg-Gly-Gly(20)-Ala-Gly-Pro-Ser-Ala-Ala-Cys-Cys-Ser-Gly(30)-Val-Arg- Ser-Leu-Lys-Ala-Ala-Ala-Ser-Thr(40)-Thr-Ala-Asp-Arg-Arg-Thr-Ala-Cys- Asn-Cys(50)-Leu-Lys-Asn-Ala-Ala-Arg-Gly-Ile-Lys-Gly(60)-Leu-Asn-Ala-Gly- Asn-Ala-Ala-Ser-Ile-Pro(70)-Ser-Lys-Cys-Gly-Val-Ser-Val-Pro-Tyr-Thr(80)- Ile-Ser-Ala-Ser-Ile-Asp-Cys-Ser-Arg-Val-Ser(91).
Arch Biochem Biophys 1988 Sep
PMID:Amino acid sequence of a probable amylase/protease inhibitor from rice seeds. 245 99


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