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)

The effects of the angiotensin converting enzyme (ACE) inhibitor captopril and the neutral endopeptidase (NEP) inhibitors thiorphan and SCH 32615 on the changes in airway opening pressure (PaO) and the recovery of offered peptide were studied after intratracheal administration of substance P (SP) and neurokinin A (NKA) in isolated guinea pig lungs superfused through the trachea. Pao changes and the recovery of offered peptide were significantly greater in NEP inhibitor-treated lungs than in control lungs. Captopril did not cause a significant change in the physiological effects or the recovery of SP and NKA. HPLC analysis of [3H]Pro2,4-SP and 125I-Histidyl1-NKA perfused through the airways showed major cleavage products consistent with NEP action. We conclude that there is significant degradation of both SP and NKA after tracheal infusion of peptides by NEP-like but not by ACE activity; this effect significantly influences the physiological effects of these peptides.
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PMID:Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs. 168 68

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

To determine the roles of endogenously released tachykinins (substance P, neurokinins A and B) in human bronchial tissues, and to determine the roles of enkephalinase (neutral endopeptidase, E.C. 3.4.24.11) in regulating the effects of the tachykinins, we studied the effects of substance P and capsaicin, which releases tachykinins, on human bronchial smooth muscle contraction in the presence or absence of enkephalinase inhibitor phosphoramidon in vitro. Substance P alone caused human bronchial smooth muscle contraction at 10(-6) M or more. Phosphoramidon (10(-7) to 10(-5) M) potentiated the substance P-induced contraction in a dose-dependent fashion, and phosphoramidon shifted the dose-response curve to lower concentrations. Capsaicin (10(-5) or 10(-4) M) alone caused bronchial smooth muscle contraction in four tissues from nine patients. After the contraction by capsaicin reached a plateau, phosphoramidon (10(-5) M) increased and prolonged the contraction significantly. Furthermore, pretreatment of bronchial tissues with phosphoramidon (10(-5) M) potentiated capsaicin-induced contraction in all tissues from five patients. Phosphoramidon (10(-5) M) shifted the dose-response curve to capsaicin to lower concentrations more than 1 log unit. Captopril did not alter the contractile response to substance P, suggesting that angiotensin-converting enzyme does not regulate the contractile response to substance P in human bronchial smooth muscle in vitro. These results suggest that enkephalinase regulates the contractile effects of exogenous substance P and endogenous substances, probably tachykinins, released by capsaicin in the human bronchus.
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PMID:Enkephalinase inhibitor potentiates substance P- and capsaicin-induced bronchial smooth muscle contractions in humans. 171 Aug 81

Luteinizing hormone-releasing hormone (LHRH) was degraded by neuronal and glial cells cultured from fetal rat brain. The degradation of LHRH by neuronal cells was strongly inhibited by a metal chelator. Captopril only inhibited by generation of fragment (1-3) from fragment (1-5). In the presence of captopril, fragment (1-5) accumulated in the highest amount among the N-terminal fragments identified. The initial cleavage of LHRH, as determined by following the loss of the LHRH peak, was strongly inhibited by thiol-blocking reagents, as well as metal chelators. The results with glial cells were almost the same as those seen with neuronal cells. Thus, we propose that a thiol-dependent membrane-bound metallo-endopeptidase plays a major role in the initial stage of degradation of LHRH at the Tyr5-Gly6 bond in both neurons and glia. Angiotensin-converting enzyme is involved in the secondary process of the LHRH degradation in both cells.
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PMID:Involvement of metallo-endopeptidase in degradation of luteinizing hormone-releasing hormone by neuronal and glial cells cultured from rat fetal brain. 201 1

The effect of peptidase inhibitors on neuropeptide release from peripheral endings of capsaicin-sensitive sensory neurons was studied in cerebral superior sagittal and transverse sinuses of guinea-pig. Capsaicin (1 microM)-evoked release of substance P-like immunoreactivity (SP-LI) was increased in a concentration-dependent manner by thiorphan (0.1-10 microM). Captopril (10 microM) or a mixture of bestatin (10 microM), leupeptin (10 microM) and bacitracin (10 microM) did not affect the capsaicin-evoked SP-LI release. Thiorphan (10 microM) increased also the capsaicin-evoked release of neurokinin A-like immunoreactivity (TK-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) by 228% and 172%, respectively, while captopril (10 microM) was without effect. Thiorphan (10 microM), but not captopril (10 microM), enhanced by 239% CGRP-LI release induced by bradykinin (10 microM). In the cerebral venous vessels neutral endopeptidase (EC 3.4.24.11, NEP)-like activity was 58.8 +/- 6.1 pmol/mg protein/min, while angiotensin converting enzyme-like activity was below the detection limit of the assay. A thiorphan-sensitive mechanism, putatively attributable to NEP, plays a major role in the inactivation of peptides released from or acting on capsaicin-sensitive sensory fibres of cerebral venous sinuses of guinea-pig.
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PMID:The effect of thiorphan on release of sensory neuropeptides from guinea-pig cerebral venous sinuses. 206 52

The hydrolysis of the porcine 26-residue brain natriuretic peptide (BNP-26) and its counterpart human 28-residue atrial natriuretic peptide (alpha-hANP) by pig membrane preparations and purified membrane peptidases was studied. When the two peptides were incubated with choroid plexus membranes, the products being analysed by h.p.l.c., alpha-hANP was degraded twice as fast as BNP. The h.p.l.c. profiles of alpha-hANP hydrolysis, in short incubations with choroid plexus membranes, yielded alpha hANP' as the main product, this having been previously shown to be the result of hydrolysis at the Cys7-Phe8 bond. In short incubations this cleavage was inhibited 84% by 1 microM-phosphoramidon, a specific inhibitor of endopeptidase-24.11. BNP-26 was hydrolysed by choroid plexus membranes, kidney microvillar membranes and purified endopeptidase-24.11 in a manner that yielded identical h.p.l.c. profiles. In the presence of phosphoramidon, hydrolysis by the choroid plexus membranes was 94% inhibited. Captopril had no effect and, indeed, no hydrolysis of BNP-26 by peptidyl dipeptidase A (angiotensin-converting enzyme) was observed even after prolonged incubation with the purified enzyme. The stepwise hydrolysis of BNP-26 by endopeptidase-24.11 was investigated by sequencing the peptides produced during incubation. The initial product resulted from hydrolysis at Ser14-Leu15, thereby opening the ring. This product (BNP') was short-lived; further degradation involved hydrolysis at Ile12-Gly13, Arg8-Leu9, Gly17-Leu18, Val22-Leu23, Arg11-Ile12 and Cys4-Phe5. Thus endopeptidase-24.11 is the principal enzyme in renal microvillar and choroid plexus membranes hydrolysing BNP-26 and alpha-hANP.
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PMID:The hydrolysis of brain and atrial natriuretic peptides by porcine choroid plexus is attributable to endopeptidase-24.11. 214 50

The metabolism of brain natriuretic peptide (BNP) was studied in rats infused with 125I-BNP. During the infusion, the intact peptide was progressively converted to labelled degradative products, separated into nine peaks of radioactivity on HPLC, and accounting for approximately 70% of total plasma radioactivity at the plateau phase. After stopping the infusion, intact BNP disappeared with a half-life of 1.23 +/- 0.35 min whereas the labelled fragments accounted for progressively greater proportion of total activity. The degradation of BNP was significantly reduced by phosphoramidon (t1/2, 11.28 +/- 0.49 min) and captopril (t1/2, 6.99 +/- 0.34 min). A maximal effect was observed when both protease inhibitors were given simultaneously (t1/2, 15.3 +/- 0.48 min). When 125I-BNP was incubated in vitro with purified endopeptidase 24.11 (E-24.11) and angiotensin-converting enzyme (ACE), there was a time-dependent disappearance of the intact peptide associated with the generation of six labelled fragments, corresponding to fragments found in vivo. In serum the peptide was rapidly degraded with a half-life of 4.6 +/- 0.1 min, and the pattern of labelled fragments was similar to that observed during in vitro incubation with ACE. Captopril significantly reduced the rate of degradation of BNP in serum. The results allow to associate two define enzyme activities, namely E-24.11 and ACE, with the metabolism of BNP in vitro. They also indicate that, despite a close homology between ANP and BNP, the two peptides undergo different pathways of clearance.
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PMID:In vivo metabolism of brain natriuretic peptide in the rat involves endopeptidase 24.11 and angiotensin converting enzyme. 217 78

To determine the role of endogenous enkephalinase (EC 3.4.24.11) in regulating peptide-induced contraction of airway smooth muscle, we studied the effect of the enkephalinase inhibitor, leucine-thiorphan (Leu-thiorphan), on responses of isolated ferret tracheal smooth muscle segments to substance P (SP) and to electrical field stimulation (EFS). Leu-thiorphan shifted the dose-response curve to SP to lower concentrations. Atropine or the SP antagonist [D-Pro2,D-Trp7,9]SP significantly inhibited SP-induced contractions in the presence of Leu-thiorphan. Leu-thiorphan increased the contractile responses to EFS dose dependently, an effect that was significantly inhibited by the SP antagonist [D-Pro2,D-Trp7,9]SP. SP, in a concentration that did not cause contraction, increased the contractile responses to EFS. This effect was augmented by Leu-thiorphan dose dependently and was not inhibited by hexamethonium or by phentolamine but was inhibited by atropine. Because contractile responses to acetylcholine were not significantly affected by SP or by Leu-thiorphan, the potentiating effects of SP were probably on presynaptic-postganglionic cholinergic neurotransmission. Captopril, bestatin, or leupeptin did not augment contractions, suggesting that enkephalinase was responsible for the effects. These results suggest that endogenous tachykinins modulate smooth muscle contraction and endogenous enkephalinase modulates contractions produced by endogenous or exogenous tachykinins and tachykinin-induced facilitation of cholinergic neurotransmission.
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PMID:Enkephalinase inhibitor potentiates substance P- and electrically induced contraction in ferret trachea. 244 55

The hydrolysis of substance P by membrane peptidases prepared from the rat substantia nigra was studied in the presence of selective inhibitors. Substance P degradation by synaptic and mitochondrial membranes was completely inhibited by 1,10-phenanthroline (1 mM), a non-specific metallopeptidase inhibitor. Captopril and bestatine, selective inhibitors of angiotensin converting enzyme and aminopeptidases respectively, were without effects. However, phosphoramidon (1 microM), a putative 'enkephalinase' inhibitor, selectively inhibited substance P degradation by synaptic membranes. These results suggest that a phosphoramidon-sensitive endopeptidase may be the principal enzyme responsible for substance P degradation in substantia nigra.
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PMID:Degradation of substance P by membrane peptidases in the rat substantia nigra: effect of selective inhibitors. 245 Mar 19


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