Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chick retina was screened for neuropeptide-metabolizing peptidase activity during development using a kininase bioassay in which hydrolysis of any peptide bond of bradykinin (Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9) leads to inactivation, combined with chromatographic bradykinin-product analysis. Bradykinin was degraded at a high rate, 6.1-26.6 mU/mg protein, by retina homogenates of all developmental stages. Kininase activity increased 2.3-fold from the 8th to the 18th embryonic day and 2-fold in the immediate posthatching period relative to the activity level at hatching. Bradykinin-product analysis, 57-113% recovery of the peptide fragments, indicated that kininase activity corresponded mostly to endopeptidase A- and to endopeptidase B-like activities (hydrolysis of Phe5-Ser6 and Pro7-Phe8 peptide bonds, respectively) and to angiotensin I-converting enzyme activity at all developmental stages. The data indicated that the relative amounts of these activities vary during retina differentiation.
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PMID:Screening for neuropeptide-metabolizing peptidases during the differentiation of chick embryo retina. 299 15

Titrations of angiotensin-converting enzyme (ACE; E.C. 3.4.15.1) present in human serum, as well as in homogenates prepared from post-mortem human caudate or mouse (C57BL1/6J) whole brain tissue, were performed with the selective ACE inhibitors, captopril (SQ 14225) and teprotide (SQ 20881). ACE activity present in human serum was more sensitive to inhibition by either inhibitor than the activity present in the brain homogenates. The inhibition curves for the titration of the human serum activity by both inhibitors were sigmoidal while the inhibition curves for the ACE activity present in the brain homogenates were more complex. These results suggest that the brain homogenates contained: at least two species of enzyme activity with properties similar to ACE but with differing affinities for the inhibitors, or substances without ACE activity that are capable of competing with ACE for the binding of the inhibitors. Therefore, measurements of captopril or teprotide-sensitive peptidase activity as well as inhibitor-binding activity may not always reflect ACE concentrations in brain tissue.
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PMID:Captopril and teprotide as discriminators of angiotensin-converting enzyme activity in brain tissue. 299 73

The investigations were carried out with partially purified angiotensin converting enzyme (E.C.3.4.15.1) from human seminal plasma and from human blood plasma. The Km-constants for angiotensin converting enzyme (ACE) from both sources, estimated by the use of synthetic substrates, were in the same order. The catalytic properties of the enzymes were characterized by a series of known peptidase inhibitors. The male antifertility drug gossypol (1,1',6,6',7,7'-hexahydroxy-3,3'-dimethyl-5,5'-bis-isopropyl-(2,2' -naphthalene)--8,8'-dicarboxaldehyde) was identified as a potent ACE-inhibitor. The inhibitory constants of several kinins and other biologically active peptides were determined. Any regulatory influence of the peptides investigated on the ACE-activity in vivo is not probably. The inhibitor of Zn-containing metalloproteases 2-(N-hydroxycarboxamido)-4-methylpentanoyl-L-alanylglycin e amide) (Zinkov) selectively inhibited ACE from blood plasma, whereas ACE from seminal plasma was not influenced. In seminal plasma the majority of the enzyme is associated with macromolecular structures, identified as membrane vesicles. These vesicles contain also other enzymatic activities usually detectable in seminal plasma. In the male genital tract ACE is synthesized in the prostate, epididymis and testis. As our data indicate ACE seems not to be involved in the regulation of sperm motility.
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PMID:Investigations on the functional role of angiotensin converting enzyme (ACE) in human seminal plasma. 302 67

The hydrolytic cleavage of angiotensin I has been studied in homogenate preparations of rat lung and aorta using gradient elution HPLC to monitor the formation of peptide products. Fresh crude homogenate preparations produced a rapid breakdown of angiotensin I to largely unidentifiable fragment peptides. Neither His-Leu nor angiotensin II was observed in these preparations even in the presence of captopril (20 microM) and the amino-peptidase inhibitors, puromycin, amastatin and bestatin. However, in freeze-thawed homogenates, angiotensin II and His-Leu were detectable together with the tetrapeptide, angiotensin (1-4). The addition of captopril (20 microM) reduced the amount of angiotensin II produced but did not completely block its formation. Higher concentrations of captopril or the addition of enalaprilat or EDTA did not further reduce the amount of angiotensin II produced. In the presence of captopril a peptide corresponding to des-Leu(10)angiotensin I was formed in relatively large amounts (equivalent to 40% of angiotensin I catabolized). Homogenates purified by concanavalin A affinity chromatography gave a clean hydrolysis of angiotensin I to angiotensin II and His-Leu which was completely blocked by captopril. These results suggest an ACE-like activity in rat lung and aorta that is not sensitive to converting enzyme inhibitors.
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PMID:Hydrolysis of angiotensin I by peptidases in homogenates of rat lung and aorta. 335 87

Although kinins have been reported to affect cerebral vascular tone and permeability, their actions are not potentiated by angiotensin converting enzyme inhibitors. To investigate cerebral vascular kinin metabolism, porcine cerebral microvessels were isolated by differential sieving and centrifugation and characterized by microscopic examination and marker enzyme enrichment. Purified microvessels contained a membrane-bound carboxypeptidase which hydrolyzed the C-terminal Phe-Arg bond of both kallidin and bradykinin. Hydrolysis was optimal at pH 7.0, was activated more than 300% by 0.1 mM CoCl2, and was inhibited by o-phenanthroline and the carboxypeptidase N (EC 3.4.17.3) inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid (MERGETPA) (IC50 = 2 microM). Conversely, inhibitors of angiotensin I converting enzyme (captopril), neutral endopeptidase (phosphoramidon), post proline cleaving enzyme (Z-Pro-prolinal), dipeptidyl(amino)peptidase IV (diprotin A) and amino-peptidase M (amastatin) had no effect. When the rates of C-terminal hydrolysis of kallidin by detergent-solubilized cerebral microvasculature were determined over a range of substrate concentrations (16.6 to 250 microM), the Km and Vmax values obtained were 26.0 +/- 3.0 microM and 14.7 +/- 1.3 nmol/min/ml (N = 4) respectively. These data suggest that a cerebral microvascular carboxypeptidase may play a role in vivo in modulating the effects of kinins on cerebral blood flow and permeability and in preventing circulating kinins from crossing the blood-brain barrier.
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PMID:Kallidin and bradykinin metabolism by isolated cerebral microvessels. 339 72

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

The contents of [Met5]-enkephalin and its four hydrolysis products, Tyr, Tyr-Gly, Tyr-Gly-Gly, and Tyr-Gly-Gly-Phe, in the sample obtained after enkephalin was incubated with tissues in either the absence or the presence of the peptidase inhibitor were estimated by high performance liquid chromatography combined with electrochemical detection in order to elucidate the effect of the peptidase inhibitor on enkephalin hydrolysis. Free Tyr was the major degradative product in the absence of the peptidase inhibitor, while the major hydrolysis product was the Tyr-Gly-Gly fragment in the presence of amastatin in both total homogenates and membrane fractions prepared from either the myenteric plexus-longitudinal muscle strip of guinea-pig ileum or the striatum of guinea-pig brain. Additionally, captopril significantly decreased the generation of Tyr-Gly-Gly in the presence of amastatin in both ileal and striatal membrane fractions. Moreover, thiorphan significantly prevented the formation of Tyr-Gly in the presence of both amastatin and captopril in both membrane preparations. Finally, when [Met5]-enkephalin was incubated with either an ileal or a striatal membrane fraction for 60 min at 37 degrees C in the presence of three peptidase inhibitors, amastatin, captopril, and thiorphan, approximately 98 or 94%, respectively, of enkephalin remained intact. The results indicated that [Met5]-enkephalin was almost exclusively hydrolyzed by three distinct enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and thiorphan-sensitive endopeptidase-24.11 in both ileal and striatal membrane fractions.
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PMID:Effects of peptidase inhibitors on the [Met5]-enkephalin hydrolysis in ileal and striatal preparations of guinea-pig: almost complete protection of degradation by the combination of amastatin, captopril and thiorphan. 353 99

Release of [Met]enkephalin immunoreactivity (Met-IR) in the central nucleus of the amygdala (ACE) was investigated in vivo in anesthetized rats implanted with push-pull cannulae. A stable spontaneous release of this peptide (1.3 fmol/15 min fraction) could be measured in the superfusates using a highly sensitive radioimmunoassay. The addition to the superfusion medium of cocktail of peptidase inhibitors increased three times the spontaneous release of the peptide. Superfusion with 30 mM potassium increased ten times the release of the peptide. Chemical stimulation of the substantia nigra with K+ enhanced four times the Met-IR release in the ipsilateral ACE. The dopaminergic component of the nigro-amygdaloid pathway appeared not to be directly implicated in this effect, since: d(+)amphetamine application in the ACE, which enhanced the local release of DA, remained without effect on Met-IR release and haloperidol-induced blockade of dopaminergic receptors in the ACE similarly did not affect Met-IR release.
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PMID:Release of [Met]enkephalin in the central nucleus of the amygdala is increased by application of potassium in the substantia nigra. 356 24

The systemic delivery of peptides and proteins from the nasal, rectal, vaginal, and buccal mucosae has been the subject of active investigation. The objective of this study was to determine the pathway and rate of hydrolysis of methionine enkephalin (TGGPM), leucine enkephalin (TGGPL), and [D-Ala2] met-enkephalinamide (TAGPM) in homogenates of these non-oral mucosae relative to the ileal mucosa. Aminopeptidases appeared to contribute over 85% to the hydrolysis of TGGPM and TGGPL, while dipeptidyl peptidase and dipeptidyl carboxypeptidase contributed much less. Overall, TGGPM was somewhat more susceptible to hydrolysis than TGGPL but was 10 times more so than TAGPM. These enkephalins were most rapidly hydrolyzed in the rectal and buccal homogenates, followed by the nasal and then the vaginal homogenates, but the differences in hydrolytic rates were small. Indeed, these rates did not differ substantially from the ileal mucosa, suggesting that the same enzymatic barrier to enkephalin absorption possibly exists in both the oral and the non-oral mucosae.
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PMID:Enkephalin hydrolysis in homogenates of various absorptive mucosae of the albino rabbit: similarities in rates and involvement of aminopeptidases. 371 36

Previous studies have shown that three distinct enzymes, amastatin-sensitive aminopeptidase, captopril-sensitive peptidyl dipeptidase A, and phosphoramidon-sensitive endopeptidase-24.11, played a critical role in the inactivation of enkephalins in isolated preparations. In the present study, therefore, the rank order of the potency of three endogenous opioid peptides, [Met5]-enkephalin, [Leu5]-enkephalin, and beta-endorphin, in three isolated preparations, guinea-pig ileum, mouse vas deferens, and rat vas deferens, was estimated in the presence of the mixture of three peptidase inhibitors, amastatin, captopril, and phosphoramidon. [Met5]-Enkephalin was approximately three-fold more potent than [Leu5]-enkephalin and four-fold more potent than beta-endorphin in guinea-pig ileum in which three opioid peptides were indicated to act on mu-receptors. Additionally, [Met5]-enkephalin was slightly but significantly more potent than [Leu5]-enkephalin and approximately twenty-fold more potent than beta-endorphin at delta-receptor sites in mouse vas deferens. Moreover, [Met5]-enkephalin was approximately three-fold more potent than [Leu5]-enkephalin, but sixty-fold less potent than beta-endorphin in rat vas deferens in which the opioid-receptor type interacting with enkephalins could not be determined. In conclusion, the well-known rank order of the potency of three endogenous opioid peptides was shown to be altered in both guinea-pig ileum and mouse vas deferens but not in rat vas deferens by the pretreatment of the preparations with the mixture of three peptidase inhibitors.
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PMID:The relative potency of enkephalins and beta-endorphin in guinea-pig ileum, mouse vas deferens and rat vas deferens after the administration of peptidase inhibitors. 376 46


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