UNIPROT:P01189 - FACTA Search

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Query: UNIPROT:P01189 (beta-endorphin)
21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The peptides alpha-MSH and MSH/ACTH 4-10 were degraded by rat brain extracts and serum to yield free amino acids among the end-products. Breakdown of these two peptides was double that of a related synthetic hexapeptide Met (0)-Glu-His-Phe-D-Lys-Phe. No significant breakdown of the hexapeptide occurred after incubation with human serum; it also had almost negligible pigmentary effects in vivo and in vitro when compared to alpha-MSH. The patterns of amino acid release indicate possible endopeptidase cleavage at Phe-Arg in alpha-MSH followed by secondary exopeptidase action to release free amino acids. For the hexapeptide, the primary cleavage point occurred at the -His3-Phe4 bond. The stability of this analog in human sera, coupled with its lower rate of degradation in the CNS, may contribute to its more potent behavioral actions in vivo.
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PMID:Biodegradation of alpha-MSH and derived peptides by rat brain extracts, and by rat and human serum. 19 Nov 54

Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.
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PMID:Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland. 127 86

Evidence supporting the concept that the parasitic trematode Schistosoma mansoni may escape immune reactions from its vertebrate (man) or invertebrate (the freshwater snail Biomphalaria glabrata) hosts by using signal molecules it has in common with these hosts was obtained by the following experiments. The presence of immunoactive proopiomelanocortin (POMC)-derived peptides [corticotropin (ACTH), beta-endorphin] in, and their release from, S. mansoni was demonstrated. Coincubation of adult worms with human polymorphonuclear leukocytes or B. glabrata immunocytes led to the appearance of alpha-melanotropin (MSH) in the medium. The conclusion that this alpha-MSH resulted from conversion of the parasite ACTH by neutral endopeptidase 24.11 (NEP) present on these cells was supported by the fact that the alpha-MSH level in the medium was markedly reduced by addition of the specific NEP inhibitor phosphoramidon. This interpretation is substantiated by the fact that no conversion was observed in comparable tests with human monocytes, which exhibit no NEP activity. alpha-MSH has the capacity to inactivate formerly active immunocytes not only from the definitive host (man, hamster) but also from the intermediate host (B. glabrata), as determined by microscopic computer-assisted examination of conformational changes. POMC-derived peptides have been detected in B. glabrata hemolymph 2, 10, and 24 days after infection by S. mansoni miracidia. Immunocytes from infected snails were found to be inactivated, and this inactivation was prevented by antibodies directed against ACTH and alpha-MSH. The immunoactive beta-endorphin released from S. mansoni does not appear to be subject to enzymatic conversion. Since it is active at lower concentrations, it may be used for distant signaling.
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PMID:Immunosuppression in the definitive and intermediate hosts of the human parasite Schistosoma mansoni by release of immunoactive neuropeptides. 130 57

The activation of human granulocytes and invertebrate immunocytes was found to be suppressed by corticotropin (ACTH) and melanotropin (MSH). In spontaneously active granulocytes both neuropeptides caused significant conformational changes indicative of inactivity plus a reduction in their locomotion. Significant inactivation of human granulocytes by ACTH required 2 hr, that by MSH only 20 min. The addition to the incubation medium of phosphoramidon, a specific inhibitor of neutral endopeptidase 24.11, blocked inactivation of granulocytes by ACTH. Radioimmunoassay for MSH of supernatant fluids from granulocytes incubated with ACTH demonstrated a time-dependent increase in MSH. These data strongly indicate that the effect of ACTH is largely due to its conversion to MSH by granulocyte-associated neutral endopeptidase. Parallel experiments with immunocytes from the mollusc Mytilus edulis gave similar results, indicating the universality of this phenomenon. Our finding that the human immunodeficiency virus, among several viruses, induces ACTH and MSH production in H9 T-lymphoma cells suggests an important role of these neuropeptides in the immunosuppression characteristic of such infections.
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PMID:Immunosuppressive effects of corticotropin and melanotropin and their possible significance in human immunodeficiency virus infection. 130 58

The effects of the opioid neuropeptide [D-Ala2]deltorphin I, isolated from amphibian skin, on immunoregulatory activities were studied in representatives of vertebrates and invertebrates. The high potency of this compound parallels that of [Met]enkephalin, which was previously demonstrated in vertebrate plasma and invertebrate hemolymph. The addition of [D-Ala2]deltorphin I at 10(-11) M to human granulocytes or immunocytes of the mollusc Mytilus edulis resulted in cellular adherence and conformational changes indicative of cellular activation. This value is in line with the concentrations obtained with [Met]enkephalin, tested in the presence of the specific neutral endopeptidase 24.11 inhibitor phosphoramidon, and this opioid's synthetic analog [D-Ala2, Met5]enkephalin which, like [D-Ala2]deltorphin I, is resistant to proteolytic degradation. Both ligands appear to be acting on the same population of immunocytes. The same relationship was estimated to exist in the insect Leucophaea maderae, in which the high viscosity of the hemolymph makes the quantification of reactive cells more difficult than in Mytilus. In addition, [D-Ala2]deltorphin I is as potent as beta-endorphin in affecting the proliferation of lymphocytes in response to mitogen. Saturation experiments with unlabeled ligands and the radioligands [3H][D-Ala2]deltorphin I and [3H][D-Ala2,Met5]enkephalinamide revealed the presence of two high-affinity binding sites on human granulocytes, one sensitive to the nonequilibrium delta opioid antagonist [D-Ala2,Leu5,Cys6]enkephalinamide and the other relatively insensitive. The results obtained with [D-Ala2]deltorphin I support the view that the special role played by endogenous [Met]enkephalin in immunobiological activities of vertebrates and invertebrates is mediated by a special subtype of delta opioid receptor.
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PMID:[D-Ala2]deltorphin I binding and pharmacological evidence for a special subtype of delta opioid receptor on human and invertebrate immune cells. 132 92

beta-Endorphin- and alpha-melanotrophin (alpha-MSH)-related peptides were extracted from the pars intermedia of Xenopus laevis maintained for 2, 4 or 6 weeks on a white background and for the same periods on a black background. The peptides were resolved under dissociating conditions by gel exclusion chromatography on Sephadex G-50 and they were detected by radioimmunoassay with antibodies to beta-endorphin, alpha,N-acetyl beta-endorphin and alpha-MSH. The beta-endorphin-related peptides separated into two fractions of different molecular size. Further purification of the peptides in each fraction was by ion exchange chromatography on SP-Sephadex C-25 and by high-pressure liquid chromatography. The alpha-MSH-related peptides were resolved by gel exclusion and ion exchange chromatography. The purified beta-endorphin- and alpha-MSH-immunoreactive peptides were identified by comparison of their chromatographic properties with the corresponding peptides from porcine pituitary or by comparison with synthetic peptides. The major form of beta-endorphin in the pars intermedia of the frog adapted to a white background was identified as alpha,N-acetyl beta-endorphin (1-8); it was accompanied by a small quantity of acetylated peptides with molecular size similar to beta-endorphin. In contrast, the pars intermedia of the frogs adapted to a black background contained approximately equal amounts of alpha,N-acetyl beta-endorphin (1-8) and the larger forms of beta-endorphin. The higher molecular weight forms were identified as the alpha,N-acetyl derivatives of beta-endorphin (1-26), (1-27) and (1-31); however after 6 weeks of white adaptation the sole remaining peptide in this group was the 26-residue peptide. An additional beta-endorphin immunoreactive peptide, provisionally identified as beta-endorphin (10-26), was present in both black- and white-adapted animals; the amounts of this peptide increased during white adaptation. Major differences in the processing of alpha-MSH were also observed. In the frogs adapted to a black background des-acetyl alpha-MSH greatly predominated over the acetyl form whereas after 6- weeks adaptation to a white background the acetylated peptide proved to be the principal component. The results demonstrate that the proteolytic processing of beta-endorphin and the acetylation of alpha-MSH in Xenopus laevis are influenced by background adaptation. The formation of beta-endorphin (1-8) appears to reflect the action of an endopeptidase that acts at the single arginine residue present at position 9.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The processing of beta-endorphin and alpha-melanotrophin in the pars intermedia of Xenopus laevis is influenced by background adaptation. 133 91

Whereas endopeptidase 24.11 cleaves the Gly-Phe bond in both Met- and Leu-enkephalin, endopeptidase 24.15 rapidly converts dynorphin A1-8, alpha and beta-neoendorphin into Leu-enkephalin, and Met-enkephalin-Arg6-Gly7-Leu8 (MERGL) into Met-enkephalin. Inhibitors of both endopeptidase 24.11 and endopeptidase 24.15 each produce antinociception, and inhibitors of endopeptidase 24.11 increase the magnitude of enkephalin antinociception. The present study compared the central antinociceptive effect of an inhibitor of endopeptidase 24.15, N-[1-(R-S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) with one of endopeptidase 24.11 N-[1-(RS)-carboxy-3-phenylpropyl]-Phe-p-aminobenzoate (cFP-F-pAB) upon central opioid antinociception induced by MERGL, metenkephalin and dynorphin A1-8. cFP-AAF-pAB, but not cFP-F-pAB increased MERGL antinociception on the tail-flick and jump tests. In contrast, cFP-F-pAB, but not cFP-AAF-pAB increased met-enkephalin antinociception. Whereas central dynorphin A1-8 failed to induce antinociception itself, co-administration of cFP-AAF-pAB and dynorphin A1-8 increased nociceptive thresholds. This effect was not accompanied by motor dysfunction, but was blocked by systemic pretreatment with naloxone or central pretreatment with naltrexone or nor-binaltorphamine, but not beta-funaltrexamine. These data indicate that endopeptidase 24.15 may be responsible for the degradation of specific opioid peptides (e.g., MERGL, dynorphin), and that this process may prevent the full expression of their antinociceptive properties.
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PMID:Endopeptidase 24.15 inhibition and opioid antinociception. 134 91

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

Neutral endopeptidase (NEP; EC 3.4.24.11) is an integral membrane protein found at the plasma membrane of many cell types. A secreted form of NEP (sec-NEP) was recently obtained by transfection of COS-1 cells with a recombinant expression vector consisting of the cDNA encoding the signal peptide of pro-opiomelanocortin fused in-frame to the cDNA sequence of the complete ectodomain of rabbit NEP [Lemay, Waksman, Roques, Crine & Boileau (1989) J. Biol. Chem. 264, 15620-15623]. In order to produce large quantities of this enzyme for structural studies we have expressed this recombinant soluble form of NEP at high yields using a baculovirus/insect-cell system. A recombinant Autographa californica nuclear polyhedrosis-virus genome containing the sec-NEP sequence was used to infect host Spodoptera frugiperda Sf9 cells. Infected cells secreted an N-glycosylated soluble form of neutral endopeptidase which was enzymically active. The yield was about 80 nmol of enzyme/litre of culture. The soluble form of the recombinant enzyme purified by immunoaffinity showed the same catalytic properties as the wild-type enzyme extracted from the kidney brush-border membranes. Treatment of the recombinant enzyme with endo-beta-N-acetylglucosaminidase H showed, however, that invertebrate cells did not glycosylate the enzyme to the same extent as did mammalian cells. Our findings demonstrate that insect cells can be used as hosts for the production of the soluble form of neutral endopeptidase. We also conclude that neither a full complement of carbohydrate side chains nor the membrane anchor appear to be essential for the production and targeting to the cell surface of a fully functional enzyme in this expression system.
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PMID:Secretion of a functional soluble form of neutral endopeptidase-24.11 from a baculovirus-infected insect cell line. 159 10

The proteolytic processing of frog (Rana esculenta) proopiomelanocortin in melanotropic cells of the intermediate pituitary gland has been examined through purification of the mature fragments by reverse-phase high-pressure liquid chromatography and microsequencing of isolated peptides. alpha-Melanotropin, beta-melanotropin, Lys-gamma-melanotropin, corticotropin-like intermediate lobe peptide, and hinge peptide have been isolated and chemically characterized. The results show a high preservation in the processing sites of frog proopiomelanotropin when compared to bovine counterparts. They reveal also a great conservation of the processing enzyme equipment of melanotropic cells in tetrapods species. Identification of Lys-gamma-melanotropin suggests the occurrence of an endopeptidase able to cleave between two basic residues. On the other hand alpha-melanotropin does not appear to be N-acetylated, as previously found in the clawed-toad Xenopus laevis, and this feature might distinguish amphibian from mammalian proopiomelanocortin processing.
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PMID:Study of frog (Rana esculenta) proopiomelanocortin processing in the intermediate pituitary. Identification of alpha-melanotropin, beta-melanotropin, Lys-gamma-melanotropin, and corticotropin-like intermediate lobe peptide. 165 Dec 91

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