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)

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.
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PMID:Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase). 152 Feb 71

It is theorized that intermediate filaments are important in the modulation of membrane activity and cell motility; however, their functions are unknown. The assembly and organization of these filaments are under hormonal regulation. We investigated in human monocytes the in vitro effects of Met-enkephalin, Leu-enkephalin, and beta-endorphin on the expression of immunoreactive cytoskeletal vimentin filaments. We simultaneously examined their effect on the phagocytosis of Candida albicans and on the membrane display of surface molecules. The three opioid peptides markedly reduced the expression of vimentin filaments, the phagocytic activity, and the display of HLA-DR molecules at concentrations of 10(-6), 10(-8), and 10(-10) M. On the other hand, the intravenous administration of fentanyl, a synthetic opiate agonist, to patients undergoing surgery induced similar changes in monocytes. In other experiments, 10(-8) M beta-endorphin also decreased the expression of CR3 but did not influence the display of CD13, a surface protein of unknown function. Expression of vimentin filaments correlated directly with the display of HLA-DR antigens and CR3 and with the phagocytic activity. The results of this paper indicate that opiates and opioids, neuropeptides known to be released during stress, can directly depress several monocyte functions. Furthermore, from these data it may be speculated that intermediate filaments may regulate the membrane expression of some surface molecules and the phagocytic process.
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PMID:Opioid peptides modulate the organization of vimentin filaments, phagocytic activity, and expression of surface molecules in monocytes. 271 83

The peptides that represent the major components with alpha-endorphin- and gamma-endorphin-like immunoreactivity in the rat neurointermediate lobe were purified to homogeneity and chemically characterized. Rat neurointermediate lobes were extracted by boiling and homogenization in acetic acid. Peptide purification was based on gel filtration, followed by two high-pressure liquid chromatography steps. Pools containing peptides with the size and immunochemical properties of alpha- and gamma-endorphins were resolved by reverse-phase high-pressure liquid chromatography into multiple immunoreactive components. The major forms were finally purified by paired-ion high-pressure liquid chromatography. The amino acid compositions of these peptides fitted the beta-endorphin sequences 1-16 and 1-17. Tryptic mapping, aminopeptidase M digestion, chromatographic characterization, and immunoreactivity to an antiserum recognizing the N alpha-acetylated terminus of endorphins showed that these peptides were indistinguishable from N alpha-acetyl-alpha-endorphin (N alpha-acetyl-beta-endorphin 1-16), and N alpha-acetyl-gamma-endorphin (N alpha-acetyl-beta-endorphin 1-17). The NH2-terminal residue of the peptides was identified by mass spectrometry as N alpha-acetyltyrosine, substantiating the identity of the peptides. The results demonstrate the existence of N alpha-acetylated alpha- and gamma-endorphin as endogenous peptides in the neurointermediate lobe of the rat pituitary gland. In view of their occurrence and biological properties they should be considered significant members of the pro-opiomelanocortin family.
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PMID:Identification of N alpha-acetyl-alpha-endorphin and N alpha-acetyl-gamma-endorphin isolated from the neurointermediate lobe of the rat pituitary gland. 286 Jan 8

Since both aminopeptidases and angiotensin I-converting enzyme are reported to degrade circulating enkephalins, we have examined the degradation of low-molecular-weight opioid peptides by a vascular plasma membrane-enriched fraction previously shown to contain both angiotensin I-converting enzyme (EC 3.4.15.1) and aminopeptidase M (EC 3.4.11.2). Except for an enkephalin analog resistant to amino-terminal hydrolysis, [D-Ala2]enkephalin, the purified vascular plasma membrane preferentially degraded low-molecular-weight opioids by hydrolysis of the N-terminal Tyr-1--Gly-2 bond. Enkephalin degradation was optimal at pH 7.0 and was inhibited by the aminopeptidase inhibitors amastatin (I50 = 0.08 microM), bestatin (9.0 microM) and puromycin (80 microM). Maximal rates of hydrolysis, calculated per mg plasma membrane protein, were highest for the shorter peptides (18.3, 15.6 and 16.6 nmol/min per mg for Met5-enkephalin, Leu5-enkephalin and Leu5-enkephalin-Arg6, respectively) and decreased with increasing peptide length (0.7 nmol/min per mg for dynorphin (1-13)). No significant hydrolysis of beta- and gamma-endorphin was detected. Km values decreased significantly with increasing peptide length (Km = 72.9 +/- 2.7, 43.6 +/- 4.7 and 21.4 +/- 0.9 microM for Met5-enkephalin, Leu5-enkephalin-Arg6 and Met5-enkephalin-Arg6-Phe7, respectively). However, no further decreases were seen with even larger sequences, i.e., dynorphin(1-13). Other peptides hydrolyzed by the plasma membrane aminopeptidase (angiotensin III, kallidin and hepta(5-11)-substance P) inhibited enkephalin degradation in a competitive manner. Thus, localization, specificity and kinetic data are consistent with identification of aminopeptidase M as a vascular enzyme with the capacity to differentially metabolize low-molecular-weight opioid peptides within the microenvironment of vascular cell surface receptors. Such differential metabolism may play a role in modulating the vascular effects of peripheral opioids.
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PMID:Degradation of low-molecular-weight opioid peptides by vascular plasma membrane aminopeptidase M. 287 42

Aminopeptidase M (EC 3.4.11.2), which can degrade low molecular weight opioid peptides, has been reported in both peripheral vasculature and in the CNS. Thus, we have studied the metabolism of opioid peptides by membrane-bound aminopeptidase M derived from cerebral microvessels of hog and rabbit. Both hog and rabbit microvessels were found to contain membrane-bound aminopeptidase M. At neutral pH, microvessels preferentially degraded low molecular weight opioid peptides by hydrolysis of the N-terminal Tyr1-Gly2 bond. Degradation was inhibited by amastatin (I50 = 0.2 microM) and bestatin (10 microM), but not by a number of other peptidase inhibitors including captopril and phosphoramidon. Rates of degradation were highest for the shorter peptides (Met5- and Leu5-enkephalin) whereas beta-endorphin was nearly completely resistant to N-terminal hydrolysis. Km values for the microvascular aminopeptidase also decreased significantly with increasing peptide length (Km = 91.3 +/- 4.9 and 28.9 +/- 3.5 microM for Met5-enkephalin and Met5-enkephalin-Arg6-Phe7, respectively). Peptides known to be present within or in close proximity to cerebral vessels (e.g., neurotensin and substance P) competitively inhibited enkephalin degradation (Ki = 20.4 +/- 2.5 and 7.9 +/- 1.6 microM, respectively). These data suggest that cerebral microvascular aminopeptidase M may play a role in vivo in modulating peptide-mediated local cerebral blood flow, and in preventing circulating enkephalins from crossing the blood-brain barrier.
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PMID:Metabolism of opioid peptides by cerebral microvascular aminopeptidase M. 287 69

The degradation of opioid peptides by human placental aminopeptidase M was studied by measuring liberated amino acids by high performance liquid chromatography. The purified placental aminopeptidase M actively degraded Met-enkephalin (Met-Enk) and Leu-enkephalin (Leu-Enk) completely into constituent 5 amino acids. The activities as a function of tyrosine liberation were observed for Met-Enk followed by Leu-Enk, beta-neoendorphin, dynorphin, and beta-endorphin.
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PMID:In vitro degradation of opioid peptides by human placental aminopeptidase M. 290 92

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

A membrane-bound aminopeptidase was purified from rat brain, and its activity was assayed by high-pressure liquid chromatography with Met-enkephalin as the substrate. The enzyme was extracted with 1% Triton X-100 and purified by chromatography, successively on DEAE-Sepharose CL-6B, Bio-Gel HTP, and Sephadex G-200 columns. The overall purification was about 1200-fold, with 25% yield. The purified enzyme showed one band on disc gel electrophoresis and two bands on sodium dodecyl sulfate electrophoresis with molecular weights of 62 000 and 66 000. The aminopeptidase has a pH optimum of 7.0, a Km of 0.28 mM, and a Vmax of 45 mumol (mg of protein)-1 min-1 for Met-enkephalin. It releases tyrosine from Met-enkephalin, but it does not split the byproduct. It does not hydrolyze gamma- or beta-endorphin, or dynorphin, but it does hydrolyze neutral and basic aminoacyl beta-naphthylamides. The enzyme is inhibited by the aminopeptidase inhibitors amastatin, bestatin, and bestatin-Gly. Its properties, such as its subcellular localization, substrate specificity, pH optimum, and molecular weight, distinguish it from leucine aminopeptidase, aminopeptidase A, aminopeptidase B, aminopeptidase M, and the soluble aminopeptidase for enkephalin degradation.
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PMID:Purification and characterization of an enkephalin aminopeptidase from rat brain membranes. 683 39