Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1-39). Fractionation by reverse-phase h.p.l.c. revealed ACTH(1-17) and their acetylated analogues. The intermediate lobe contained NO-diacetyl-ACTH-(1-13)-NH2, N-acetyl-ACTH-(1-13)-NH2 and ACTH-(1-13)-NH2. In addition, the corresponding ACTH-(1-14) peptides (the glycine-extended precursor of the amidated peptides) were detected in lower amounts in both the intermediate lobe and the anterior lobe. ACTH-(1-17), ACTH-(1-13) and their acetylated analogues could not be detected in the anterior lobe or the intermediate lobe. The results suggest that an endopeptidase initially cleaves ACTH-(1-39) at the Lys-16-Arg-17 bond. ACTH-(1-16) is then processed by a pituitary carboxypeptidase to ACTH-(1-14) and ACTH-(17-39) by the aminopeptidase to ACTH-(18-39).
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PMID:alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary. 301 6

A human brain aminopeptidase, which hydrolyses low molecular weight enkephalin-containing peptides (ECPs), was purified to apparent homogeneity from the homogenate of human brain. The enzyme purification involved DEAE-cellulose chromatography and preparative polyacrylamide gel electrophoresis. The purified aminopeptidase hydrolyses only the Tyr1-Gly2 bond of enkephalines and of ECPs. The rate of hydrolysis of Met-enkephalin and Leu-enkephalin was higher than the rate of hydrolysis of ECPs containing 7 to 13 aminoacid residues. Large ECPs such as peptide E and beta-endorphin were not hydrolysed. The molecular weight of this enzyme is about 100,000 daltons, as determined by gel filtration on Sephadex G-200 and by polyacrylamide gel electrophoresis in presence of sodium dodecyl sulfate. The enzyme has an isoelectric point of pH 4.9, is activated by dithiothreitol (DTT) and inhibited by puromycin, bacitracin, p-mercuryacetate, Zn++, Cu++ and Ni++. The optimum pH for enzyme activity is 7.5.
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PMID:Isolation and characterization of human brain aminopeptidase which hydrolysis enkephalin-containing peptides. 318 70

Actinonin, previously isolated as an antibiotic and shown to be an inhibitor of aminopeptidase M (EC 3.4.11.2), has now been shown to inhibit three enkephalin-degrading enzymes from guinea-pig striatum. The values of IC50 were 0.39 microM for striatal membrane aminopeptidase ("enkephalin-aminopeptidase") and 5.6 microM striatal membrane neutral endopeptidase ("enkephalinase A"). Furthermore, soluble dipeptidylaminopeptidase in a rat whole brain homogenate was also inhibited by actinonin with the IC50 value of 1.1 microM. Actinonin administered intracisternally (i.cist., 50 micrograms) or intraperitoneally (i.p., 100 mg/kg), potentiated the analgesic action of met-enkephalin (50 micrograms i.cist.). analgesia by a tail-flick test. The potentiating activity of actinonin i.p. to met-enkephalin analgesia was almost the same potency as that of thiorphan, whereas the inhibitory activity of actinonin against enkephalinase A was 1/1000 that of thiorphan. Actinonin alone, administered either i.cist. or i.p., showed an analgesic action as estimated by the tail-flick test.
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PMID:Analgesic effect of actinonin, a new potent inhibitor of multiple enkephalin degrading enzymes. 329 9

Biotransformation of [3H-Lys9] DE gamma E was investigated after in vitro incubation of the tritiated peptide with rat, dog and human plasma. In addition, its metabolite profile in blood was studied following intravenous administration to rats and dogs. Half-lives for the in vitro disappearance of DE gamma E in plasma were 13.0 +/- 0.8 min (dog), 15.7 +/- 1.2 min (rat) and 19.2 +/- 0.9 min (human), indicating very rapid degradation of the peptide by proteolytic enzymes. Biotransformation products were identified on the basis of co-chromatography on HPLC with synthetic reference peptides. The six principal fragments appeared to be beta-endorphin (beta E) sequences 7-17, 8-17, 9-17, 6-15, 7-15 and 8-15. The abundance of beta E6-15, beta E7-15 and beta E8-15 in rat and human plasma suggests preferential, subsequent carboxypeptidase and aminopeptidase mechanisms, whereas in dog plasma DE gamma E is predominantly degraded by aminopeptidase activities (major peptide metabolites: beta E7-17 and beta E8-17). In the in vivo studies with rats and dogs the same radioactive peptide fragments were detected in blood as found in the in vitro experiments with plasma. In both species their blood levels were already maximal within a minute after intravenous administration of the parent peptide, thereafter they declined rapidly. 3H-Lysine was the main radioactive metabolite in vivo, exceeding 70% of total radioactivity in rat and dog blood 10 min after 3H-DE gamma E dosing.
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PMID:Des-enkephalin-gamma-endorphin (DE gamma E): biotransformation in rat, dog and human plasma. 358 24

Blood-brain barrier (BBB) aminopeptidase activity was investigated using an in vitro model consisting of primary cultures of brain microvessel endothelium. Using two different substrates, both membrane-bound and soluble aminopeptidases were found to be associated with brain endothelium. That the enzyme activity was aminopeptidase activity was confirmed with the competitive inhibition of substrate degradation by typical aminopeptidase inhibitors puromycin and bestatin. The aminopeptidase activity was also competitively inhibited by enkephalin, met-enkephalin, and leu-enkephalin. Results from parallel experiments with cerebral gray matter and kidney confirm assay conditions. This report supports previous suggestions that aminopeptidases of the enzymatic BBB may play a role in regulating levels of circulating neuropeptides in the cerebrovasculature.
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PMID:Characteristics of aminopeptidase activity from bovine brain microvessel endothelium. 369 37

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

The effects of nineteen AHPA* derivatives were examined on morphine analgesia by tail-flick test in rats and on enkephalinase inhibition which was based on the formation of tyrosyl-glycyl-glycine from met-enkephalin. The correlation between the enhancement of morphine analgesia in vivo and enkephalinase inhibition in vitro was analyzed. The different analogs varied considerably in the degree of enhancement of morphine analgesia and inhibition of enkephalinase. A close relationship between enkephalinase inhibition expressed by IC50 in vitro and enhancement of morphine analgesia in vivo was observed in thirteen out of nineteen AHPA derivatives examined. One of other six AHPA derivatives which showed weak effectiveness in potentiating on morphine analgesia but was highly potent as an enkephalinase inhibitor, caused potent analgesic action when it was applied intracisternally indicating poor penetration of the blood brain barrier. The possibility was discussed that some of other compounds excluded from the linear relationship might act on other enkephalin degrading enzymes such as aminopeptidase.
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PMID:Relationship between enhancement of morphine analgesia and inhibition of enkephalinase by 2S, 3R 3-amino-2-hydroxy-4-phenylbutanoic acid derivatives. 612 60

When deplasticized Epon sections were treated with endo- and/or exopeptidases prior to incubation with antibodies, the neuropeptide immuno-reactivity of secretory nerves was often altered in a predictable way. Cleavage of neurosecretory material in octopus nerves by trypsin and carboxypeptidase-B enhanced enkephalin-like immunoreactivity, while Molluscan neuropeptide-like immunoreactivity was prevented by tryptic cleavage. The enzyme effects indicated the occurrence of a heptapeptide (Tyr-Gly-Gly-Phe-Met/Leu-Arg-Phe) that contains both the enkephalin and the Molluscan neuropeptide sequence. Vasopressin terminals of the rat neurohypophysis, which presumably contain enkephalin precursor sequences, exhibited enkephalin-like immunostaining after tryptic cleavage. ACTH/beta-endorphin cells of the rat intermediate pituitary, which synthesize the enkephalin sequence at the N-terminus of Beta-endorphin, exhibited enkephalin=like immunoreactivity when sections were treated with alpha-chymotrypsin or trypsin, but not after incubation with leucine-aminopeptidase or carboxypeptidase-B. Enkephalin-like immunostaining could not be induced in any way in ACTH/beta-endorphin cells of the anterior pituitary. Enzymatic cleavage may give additional information in immunocytochemical localization studies on neuropeptide sequences in secretory nerves and hormonal granules.
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PMID:Enzymatic cleavage prior to antibody incubation as a method for neuropeptide immunocytochemistry. 628 42

The action of brain peptidases on NH2-terminal sequences of adrenocorticotropin was studied by incubation of ACTH-(1-16)-NH2 under different pH conditions. Profiles of metabolites and time course of product formation were obtained by HPLC analysis of the digests. Fragments of ACTH-(1-16)-NH2 were isolated and characterized by their amino acid composition and NH2-terminal groups. Both at pH 7.4 and pH 8.5 the following fragments were found: ACTH-(3-16)-NH2, ACTH-(4-16)-NH2, ACTH-(5-16)-NH2, and ACTH-(7-16)-NH2. At pH 7.4 the major products were ACTH-(4-16)-NH2 and ACTH-(7-16)-NH2, while the peptide ACTH-(3-16)-NH2 was the main metabolite at pH 8.5. The nature of identified peptides and the time course of their formation demonstrates that aminopeptidase activities predominate in the conversion of the NH2-terminus of adreno-corticotropin and related peptides by brain synaptic membranes.
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PMID:Action of peptidases in brain synaptic membranes on the NH2-terminus of adrenocorticotropin using ACTH-(1-16)-NH2 as a model substrate. 629 90

L-Leucinal, a transition state analog inhibitor or kidney leucine amino-peptidases, was found to serve as a competitive inhibitor of soluble aminopeptidase activity from rat brain (Ki = 22 microM). Simultaneous intracisternal administration of leucinal and leu-enkephalin produced dose-dependent analgesia in the hot plate test in mice, in concentrations at which neither L-leucinal nor leu-enkephalin alone elicited a significant response. simultaneous administration of leucinal and beta-endorphin also resulted in potentiation of beta-endorphin's analgesic activity. Leucinal did not enhance the antinociceptive response to neurotensin or to [D-ala2]-met-enkephalinamide, which are structurally resistant to the action of brain aminopeptidases.
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PMID:Leucinal inhibits brain aminopeptidase activity and potentiates analgesia induced by leu-enkephalen. 664 14


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