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)

Modulation of baroreceptor reflex (BRR) by endogenous substance P (SP) in the brain was investigated in rats anesthetized with pentobarbital sodium. Intracerebroventricular administration of the undecapeptide (15 or 30 nmol) and its antagonist, (D-Pro2, D-Trp7,9)-SP (30 or 60 nmol) or SP antiserum (1:20), respectively, promoted a significant increase and decrease in the sensitivity of BRR response. Prolonging the endogenous activity of SP with the aminopeptidase blocker, bestatin (200 nmol) or with the endopeptidase-24.11 inhibitor, phosphoramidon (200 nmol) significantly augmented the same reflex. Combining the undecapeptide with either peptidase blocker, moreover, promoted additional potentiation of the BRR response. On the other hand, simultaneous administration of bestatin and (D-Pro2, D-Trp7,9)-SP produced a reduction of the augmented effect of bestatin on the sensitivity of BRR response. Bilateral microinjection of SP (600 pmol) or an antiserum against SP (1:20) into the nucleus tractus solitarius (NTS) elicited respectively an enhancement of and reduction in the BRR response. These data suggest that neurons that contain SP may participate in central cardiovascular control by tonically enhancing the sensitivity of the BRR response, possibly via an action on the NTS.
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PMID:Tonic enhancement of the sensitivity of baroreceptor reflex response by endogenous substance P in the rat. 169 52

Studies on the effects of peptidase inhibitors on substance P-like immunoreactive material (SPLI) released by K(+)-induced depolarization from slices of the rat spinal cord showed that bacitracin was the most potent agent to protect SPLI from degradation. Captopril and thiorphan which inhibit, respectively, angiotensin I converting enzyme and endopeptidase-24.11 also protected SPLI from degradation. However other inhibitors of these two enzymes, kelatorphan for endopeptidase-24.11 and enalaprilat for angiotensin I converting enzyme were essentially inactive, indicating that both enzymes are probably not involved in the degradation of endogenous substance P. Instead, the non-additive protecting effect of bacitracin, captopril and thiorphan might be due to the blockade of some 'bacitracin-sensitive enzyme' playing a key role in the catabolism of SP within the rat spinal cord.
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PMID:Is substance P released from slices of the rat spinal cord inactivated by peptidase(s) distinct from both 'enkephalinase' and 'angiotensin-converting enzyme'? 170 69

The effects of peptidase inhibitors were examined upon behavioural responses including scratch, bite and lick produced by intrathecal (IT) injection of substance P (SP) and neurokinin A (NK A) in mice. Phosphoramidon (0.002-2.0 nmol), an endopeptidase-24.11 inhibitor, simultaneously injected with SP or NK A, remarkably enhanced and prolonged SP- or NK A-induced behavioural response in a dose-dependent manner. The behavioural response to SP was significantly increased by 2.0 nmol of bestatin, an aminopeptidase inhibitor, but not by 1.0 nmol. Captopril, an angiotensin-converting enzyme inhibitor, was without effect on both tachykinin-induced responses. When phosphoramidon was injected together with bestatin and captopril which have no significant effect alone, SP- or NK A-induced behavioral response was significantly increased. These data suggest that endopeptidase-24.11 may be an important enzyme responsible for terminating of SP- or NK A-induced behavioral response at the spinal cord level.
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PMID:Phosphoramidon potentiates mammalian tachykinin-induced biting, licking and scratching behaviour in mice. 170 5

Neutral endopeptidase (NEP; EC 3.4.24.11) is well recognized as a regulatory peptidase for substance P (SP)-induced responses in various tissues. To determine whether NEP regulates SP-induced activation of human neutrophils, we examined the effect of the NEP inhibitor phosphoramidon on SP-induced superoxide generation and chemotaxis in human blood neutrophils. SP (10(-6)-10(-4) M) induced superoxide generation and chemotaxis in the neutrophils dose dependently. The NEP inhibitor enhanced the SP-induced responses. Thus, phosphoramidon (10(-6) M) shifted the dose-response curves of SP-induced superoxide generation and chemotaxis of the neutrophils to the left by 0.5-0.6 log. Phosphoramidon prevented the hydrolysis of SP by the neutrophils, the NEP activity of the neutrophils being assessed as 125 +/- 13 pmol of SP/min/10(6) cells. The N-terminal peptide SP (up to 3 x 10(-4) M), which was a major degrading product by NEP of the neutrophils, did not activate the neutrophils. We conclude that NEP modulates SP-induced activation of human neutrophils.
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PMID:Neutral endopeptidase modulates substance P-induced activation of human neutrophils. 171 1

Enkephalinase (EC 3.4.24.11, membrane metalloendopeptidase) is a zinc peptidase expressed by neurons and a variety of epithelial cells, and responsible for the inactivation of enkephalins in brain. Its functions in the gastrointestinal (GI) tract are less well understood although enkephalinase inhibitors were reported to induce a constellation of antisecretory and motor responses. Its localisation in various segments of the rat GI tract was established autoradiographically using a 125I-labelled monoclonal antibody. All along the GI tract, the highest immunoreactivity was found in mucosal layers e.g., in intestinal villi, basal epithelial layers of the oesophagus or gastric cardia, muscularis mucosae of the stomach and large intestine. The immunoreactivity was also high in the stomach submucosae and moderate in the muscularis propria of the caecum. A faint patchy immunoreactivity was also observed in several other layers. This distribution suggests that the membrane peptidase is expressed by enterocytes and a variety of other cells. Its high expression in mucosal layers is consistent with its participation in protein digestion and also in the inactivation of endogenous peptides, particularly the enkephalins, acting at this level to control secretory mechanisms and hydroelectrolytic fluxes. Its presence in submucosal layers may account for some naloxone-reversible motor responses elicited by enkephalinase inhibitors.
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PMID:Immunoautoradiographic localisation of enkephalinase (EC 3.4.24.11) in rat gastrointestinal tract. 171 43

The physiological effects of the tachykinin peptides substance P (SP) and neurokinin A (NKA) are limited by their microenvironmental degradation. We used the isolated tracheally superfused guinea pig lung to examine the importance of various degradative enzymes in limiting the physiological effects of exogenously administered and endogenously released tachykinins. When SP and NKA are administered via the airway epithelium, neutral endopeptidase (NEP; EC 3.4.24.11) is the major degradative enzyme as indicated by the effects of NEP inhibitors alone compared to the effects of a NEP inhibitor along with a cocktail of other peptidase inhibitors. The effects of enzyme inhibitors on physiological responses is mirrored in the amounts of peptide recovered from lung perfusates as determined using an enzyme-linked immunosorbent assay. We found similar effects when SP and NKA were released endogenously by the acute infusion of capsaicin. These data indicate that NEP is the predominant degradative enzyme modulating the effects of SP and NKA administered via the airways.
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PMID:Peptidase modulation of the pulmonary effects of tachykinins. 171 94

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

An endopeptidase was isolated from Xenopus laevis skin secretions. This enzyme, which has an apparent molecular mass of 100 kDa, performs a selective cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond (Xaa = Ser, Phe, Tyr, His, or Gly) of a number of peptide hormones, including atrial natriuretic factor, substance P, angiotensin II, bradykinin, somatostatin, neuromedins B and C, and litorin. The peptidase exhibited optimal activity at pH 7.5 and a Km in the micromolar range. No cleavage was produced in vasopressin, ocytocin, minigastrin I, and [Leu5]enkephalin, which include in their sequence an Xaa-Phe, Xaa-Leu, or Xaa-Ile motif. The endopeptidase activity was inhibited by divalent cation chelators and by phosphoramidon only at high concentrations (IC50 = 50 microM), whereas it was insensitive to classical inhibitors of chymotrypsin, angiotensin convertase, and serine and cysteine peptidases, as well as carboxypeptidases. It is hypothesized that this enzyme, which is distinct from neutral endopeptidase (EC 3.4.24.11), constitutes the prototype of a family of related metalloendopeptidases that inactivate peptide substrates by cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond.
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PMID:A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion. 172 23

We have demonstrated that the isolated perfused rat mesenteric arterial bed (MAB) secretes peptidases capable of metabolizing bradykinin and angiotensin I. The major degradative pathway of bradykinin by enzymes found in the rat MAB perfusate was mediated by carboxypeptidase A-like activity, whereas angiotensin 1 degradation followed two main routes, one attributable to a carboxypeptidase A-like enzyme and the other to an endopeptidase. This latter enzyme seems to be a novel serine peptidase capable of releasing angiotensin II directly from both angiotensin I and renin substrate tetradecapeptide. The rat MAB perfusate was also shown to contain additional endo- and exopeptidases that might play a role in the metabolism of other vasoactive peptides. Our finding that isolated rat MAB secretes peptidases into the perfusion medium indicates that peptide processing within the microvasculature environment may be effected by enzymes besides those normally found in plasma or associated with cell membranes.
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PMID:A survey of vasoactive peptide metabolizing enzymes in the rat mesenteric arterial bed perfusate. 174 67

The inhibitory effect of various dipeptides on the neurotensin-degrading metallopeptidase, endopeptidase 24.16, was examined. These dipeptides mimick the Pro10-Tyr11 bond of neurotensin that is hydrolyzed by endopeptidase 24.16. Among a series of Pro-Xaa dipeptides, the most potent inhibitory effect was elicited by Pro-Ile (Ki approximately 90 microM) with Pro-Ile greater than Pro-Met greater than Pro-Phe. All the Xaa-Tyr dipeptides were unable to inhibit endopeptidase 24.16. The effect of Pro-Ile on several purified peptidases was assessed by means of fluorigenic assays and HPLC analysis. A 5 mM concentration of Pro-Ile does not inhibit endopeptidase 24.11, endopeptidase 24.15, angiotensin-converting enzyme, proline endopeptidase, trypsin, leucine aminopeptidase, pyroglutamyl aminopeptidase I and carboxypeptidase B. The only enzyme that was affected by Pro-Ile was carboxypeptidase A, although it was with a 50-fold lower potency (Ki approximately 5 mM) than for endopeptidase 24.16. By means of fluorimetric substrates with a series of hydrolysing activities, we demonstrate that Pro-Ile can be used as a specific inhibitor of endopeptidase 24.16, even in a complex mixture of peptidase activities such as found in whole rat brain homogenate.
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PMID:Specific inhibition of endopeptidase 24.16 by dipeptides. 176 Oct 32


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