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)

We have investigated the pharmacological profile of the opioid stimulation of adenylate cyclase activity in rat olfactory bulb, in order to identify the opioid receptor subtype(s) involved in this response. The synthetic delta-selective agonists (D-Ala2)deltorphin I, (2-D-penicillamine,5-D-penicillamine)-enkephalin, and (D-Ser-Leu5-enkephalyl)-threonine were effective stimulators of the enzyme activity, with EC50 values of 6.7, 420, and 63 nM, respectively. A significant increase was also observed with the mu-selective agonists (N-methyl-Phe3,D-Pro4)-morphiceptin, dermorphin, and (D-Ala2-N-methyl-Phe4-Gly-ol5)-enkephalin (DAGO). The latter two agonists displayed biphasic concentration-response curves, with high affinity components accounting for 75-80% of the maximal responses. The kappa-selective agonists U-50,488 and U-69,593 were ineffective, whereas (D-Ala2)dynorphin A-1-11, dynorphin A, dynorphin A-1-13, and dynorphin A-1-6 acted with a rank order of potency consistent with their affinity for delta receptors. The stimulatory responses of Leu-enkephalin, beta-endorphin, dynorphin A, and delta-selective agonists were counteracted by naltrindole with pA2 values of 9.39-8.93, whereas naloxone was less potent (pA2 = 8.17-7.59). The kappa-selective antagonist norbinaltorphimine was the least potent. The inhibition by naltrindole and naloxone of DAGO stimulation showed biphasic curves, with 90% of the response being antagonized more potently by naloxone than by naltrindole. These results demonstrate that delta- and mu- but not kappa-opioid receptor subtypes stimulate basal adenylate cyclase activity in rat olfactory bulb.
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PMID:Characterization of opioid receptors mediating stimulation of adenylate cyclase activity in rat olfactory bulb. 132 51

The central enzymatic stability of des-enkephalin-gamma-endorphin and its synthetic analogs [cycloN alpha 6, C delta 11]beta-endorphin-[6-17] and [Pro7, Lys(Ac)9]-beta-endorphin[6-17] was studied in vitro using a newly developed, regionally dissected rat brain slice, time course incubation procedure. Tissue slice viability was estimated as the ability of the brain slice to take up or release gamma-[3H]aminobutyric acid after high K+ stimulation. Results demonstrated stability of uptake/release up to 5 hr of incubation, suggesting tissue viability over this period. The estimated half-life of peptides based on the results obtained in our incubation protocol suggest that the peptides studied are metabolized at different rates in the individual brain regions tested. A good correlation exists between the high enzyme activity of neutral endopeptidase (EC 3.4.24.11) and the rapid degradation of des-enkephalin-gamma-endorphin and [cycloN alpha 6, C delata 11]beta-endorphin-[6-17] in caudate putamen. Proline substitution combined with lysine acetylation appears to improve resistance to enzymatic metabolism in caudate putamen and hypothalamus. However, cyclization of des-enkephalin-gamma-endorphin forming an amide bond between the alpha-NH2 of the N-terminal threonine and the gamma-COOH of glutamic acid did not improve peptide stability in any brain region tested. The present study has shown that the brain slice technique is a valid and unique approach to study neuropeptide metabolism in small, discrete regions of rat brain where peptides, peptidases and receptors are colocalized and that specific structural modifications can improve peptide stability.
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PMID:Neuropeptide processing in regional brain slices: effect of conformation and sequence. 214 Jan 32

A partially purified fraction of extracted porcine pituitary glands which possesses lipolytic and adrenocorticotropic activity has been characterised. It consists of six adrenocorticotropin(ACTH)-like peptides (five of which have not been previously described) which were each purified by sequential reverse-phase (rp) HPLC. Their complete primary structures were determined following amino acid compositional analysis, extensive peptide mapping and partial sequencing. Four of the fragments represent the following ACTH fragments; ACTH(1-31), ACTH(7-34), ACTH(7-36) and ACTH(7-38). By combined analytical rpHPLC and an ACTH radioimmunoassay (with an antiserum exhibiting full cross-reaction with all six ACTH variants isolated here), evidence was obtained from analysis of extracts of whole pituitary that these fragments of ACTH exist in significant amounts relative to intact ACTH(1-39). This suggests that ACTH can undergo more extensive differential proteolytic processing than previously thought. These peptides were found to possess reduced or a complete absence of ACTH-like biological activity. Therefore the biological significance of this processing needs to be resolved. The other two fragments also resembled fragments of ACTH but each possessed the same, single amino acid substitution: a threonine replacing the arginine at the position corresponding to position 8 in the ACTH sequence and had the structures [Thr8]ACTH(1-31) and [Thr8]ACTH(7-31). They possess little ACTH-like biological activity. If these variants are derived from a variant ACTH, this would be a significant finding in view of the site of the amino acid substitution and the highly conserved nature of the ACTH primary structure. The possible physiological and genetic implications are briefly discussed. In this study attempts were also made to identify the DNA coding for the mutant ACTH sequence.
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PMID:Isolation and full structural characterisation of six adrenocorticotropin-like peptides from porcine pituitary gland. Identification of three novel fragments of adrenocorticotropin and of two forms of a novel adrenocorticotropin-like peptide. 217 74

A thiolprotease from rat brain membranes was shown to convert synthetic dynorphin B-29 (Dyn B-29, "leumorphin") to the tridecapeptide dynorphin B (Dyn B, "rimorphin"). This represents a "single-arginine cleavage" between threonine-13 and arginine-14 of the substrate. The dynorphin converting activity displayed typical Michaelis-Menten kinetics with an apparent Km for the substrate of 0.58 microM. Surprisingly, a synthetic peptide, Dyn B-29-(9-22), which contains the cleavage site, did not inhibit the activity. Dyn A inhibited the activity competitively with an apparent Ki of 3.7 microM. The converting activity was also inhibited by Dyn A-(6-17) but not by Dyn A-(8-17), suggesting a role of Arg6-Arg7 in the inhibition of converting activity. Bovine adrenal medulla Peptide E inhibited the converting activity substantially whereas metorphamide did not, suggesting the importance of COOH-terminal residues in recognition. Beta-Endorphin was an effective inhibitor of converting activity, and [alpha-N-acetyl]beta-endorphin was not, indicating a crucial role of the free NH2-terminus in recognition by the enzyme. ACTH inhibited the activity competitively with an apparent Ki of 39 nM. The converting activity was also inhibited substantially by ACTH-(1-13) but not by alpha-MSH, again indicating a requirement of the free NH2-terminus for recognition. The above results suggest that the converting enzyme recognizes peptides of the three known opioid gene families.
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PMID:Opioid and other peptides as inhibitors of leumorphin (dynorphin B-29) converting activity. 301 92

Beta-endorphin has been isolated from equine pituitaries. Its amino acid sequence is identical to that of ovine, bovine and camel beta-endorphins except for substitution of the threonine residue at position 6 by serine. The equine beta-endorphin has also been synthesized by the solid-phase method. In comparison with the human hormone, equine beta-endorphin was shown to possess 3 times the receptor-binding activity in rat membrane preparations and 1.6 times the analgesic potency in the mouse tail-flick assay.
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PMID:beta-Endorphin: isolation, amino acid sequence and synthesis of the hormone from horse pituitary glands. 628 Dec 4

The NH2-terminal domain of pro-opiomelanocortin, designated as the 16-kDa fragment, is highly conserved throughout the vertebrate family and is likely therefore to have an important functional role. Bovine 16-kDa fragment is a 77- residue glycopeptide, which has been found to be glycosylated at threonine 45 and asparagine 65. Available evidence suggests that glycoforms lacking glycans at the O-linked site are processed in the intermediate pituitary at -Arg49-Lys50- to give the residue 1-49 amino-terminal peptide and a carboxyl-terminal glycopeptide referred to as Lys1 gamma 3-melanotropin. Glycoforms carrying O-glycans remain unprocessed in the intermediate pituitary. Thus O-glycosylation is likely to play an important role in controlling the fate of the NH2-terminal portion of pro-opiomelanocortin, thereby affecting the biological events that are influenced by peptides and glycopeptides derived from this domain. In a recent study (Siciliano, R. A., Morris, H. R., McDowell, R. A., Azadi, P., Rogers, M. E., Bennett, H. P. J., and Dell, A. (1993) Glycobiology 3, 225-239), we sequenced the N-glycans attached to Asn-65 of bovine 16-kDa fragment and demonstrated that the acidic components contain, in addition to neutral antennae, a single SO4-4GalNAc beta 1-4GlcNAc beta 1- antenna, which is characteristic of the pituitary glycohormone N-glycans (Baenziger, J. U., and Green, E. D. (1988) Biochim. Biophys. Acta 947, 287-306). We now report the structural characterization of the O-linked oligosaccharides found in bovine 16-kDa fragment. The major component, which constitutes about 80% of the O-glycan population, is a novel sulfated tetrasaccharide, which carries the same sulfated epitope as the N-glycans. This is the first time that the SO4-4GalNAc beta 1-4GlcNAc beta 1- moiety has been observed in O-glycans, and it raises the interesting possibility that the beta-N-acetylgalactosaminyltransferase responsible for the addition of N-acetylgalactosamine to the pituitary glycohormones (Smith, P. L., and Baenziger, J. U. (1988) Science, 242, 930-933) might be capable of glycosylating both N- and O-linked acceptors.
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PMID:O-glycosylation mimics N-glycosylation in the 16-kDa fragment of bovine pro-opiomelanocortin. The major O-glycan attached to Thr-45 carries SO4-4GalNAc beta 1-4GlcNAc beta 1-, which is the archetypal non-reducing epitope in the N-glycans of pituitary glycohormones. 750 11

Recently, the natural vesicant cantharidin was shown to bind exclusively to and inhibit protein phosphatase 2A (PP2A) in mouse tissue extracts (Li and Casida (1992) Proc. Natl. Acad. Sci. USA 89, 11867-11870). To explore the generality of this effect in vesicant action, we measured the protein serine/threonine phosphatase activity in mouse liver cytosol (in the form of the okadaic acid inhibitable increment of p-nitrophenyl phosphate (p-NPP) phosphatase activity) in the presence of aqueous sulfur mustard or its hydrolysis product, bis(hydroxyethyl)sulfide (TDG). Sulfur mustard inhibited p-NPP hydrolysis. However, inhibition correlated with the time elapsed between thawing and the addition of mustard to the enzyme preparation, not with concentration. TDG exhibited a direct, concentration-related inhibition of p-NPP hydrolysis between 30 and 300 microM. We conclude that sulfur mustard also has an inhibitory effect on protein serine/threonine phosphatases. However, the inhibition is an effect of its non-alkykating hydrolysis product TDG, not of sulfur mustard itself.
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PMID:Possible protein phosphatase inhibition by bis(hydroxyethyl)sulfide, a hydrolysis product of mustard gas. 760 98

A study of bovine adrenocortical cell shape on adrenocorticotropic hormone (ACTH) challenge showed that the cells round up and develop arborized processes. This effect was found to be (1) specific for ACTH because angiotensin II and basic fibroblast growth factor have no effect; (2) mediated by a cAMP-dependent pathway because forskolin reproduces the effect of the hormone; (3) inhibited by sodium orthovanadate, a phosphotyrosine phosphatase inhibitor, but unchanged by okadaic acid, a serine/threonine phosphatase inhibitor; and (4) correlated with a complete loss of focal adhesions. Biochemical studies of the focal-adhesion-associated proteins showed that pp125fak, vinculin (110 kDa) and paxillin (70 kDa) were detected in the Triton X-100-insoluble fraction from adrenocortical cells. During cell adhesion on fibronectin as substratum, two major phosphotyrosine-containing proteins of molecular masses 125 and 68 kDa were immunodetected in the same fraction. A dramatic decrease in the extent of tyrosine phosphorylation of these proteins was observed within 60 min after treatment with ACTH. No change in pp125fak tyrosine phosphorylation nor in Src activity was detected. In contrast, paxillin was found to be tyrosine-dephosphorylated in a time-dependent manner in ACTH-treated cells. Sodium orthovanadate completely prevented the effect of ACTH. These observations suggest a possible role for phosphotyrosine phosphatases in hormone-dependent cellular regulatory processes.
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PMID:Hormonal regulation of focal adhesions in bovine adrenocortical cells: induction of paxillin dephosphorylation by adrenocorticotropic hormone. 960 Oct 84

Live T. cruzi trypomastigotes and amastigotes possess ecto-protein tyrosine phosphatase activity as indicated by the ability of intact cells to catalyze dephosphorylation of tyrosine phosphorylated myelin basic protein, [32P]TyrRaytide, phosphotyrosine, or the phosphotyrosine analog p-nitrophenylphosphate (p-NPP). The dephosphorylation of myelin basic protein (MBP) and p-NPP was inhibited by sodium o-vanadate, zinc chloride and NaF, while dephosphorylation of [32P]TyrRaytide was insensitive to zinc chloride but sensitive to o-vanadate and NaF. In contrast, live cells were not able to dephosphorylate serine or threonine phosphorylated peptides ([32P]Kemptide) or proteins ([32P]RCM-lysozyme and [32P]MBP).
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PMID:Ecto-protein tyrosine phosphatase activity in Trypanosoma cruzi infective stages. 965 37

Corticotropin signal transduction pathway involves serine/threonine protein phosphorylation. Recent reports suggest that protein tyrosine dephosphorylation may also be an integral component of that pathway. The present study was performed to investigate the role played by protein tyrosine phosphatases (PTPs) on acute response to corticotropin and the hypothetical regulation of PTPs by this hormone. We have used two powerful cell permeant PTP inhibitors, phenylarsine oxide (PAO) and pervanadate (PV), in order to examine the relevance of PTP activity on hormone-stimulated and 8-bromo-adenosine 3',5'-phosphate (8Br-cAMP is a permeant analogue of adenosine 3',5'-phosphate)-stimulated steroidogenesis in adrenal zona fasciculata (ZF) cells. In both cases, PAO and PV inhibited the steroid production in a dose-dependent fashion, and had no effect on steroidogenesis supported by a permeant analogue of cholesterol. The effect of hormonal stimulation on PTP activity was analyzed in rat adrenal ZF. In vivo corticotropin treatment reduced phosphotyrosine content in endogenous proteins and produced a transient increase of PTP activity in the cytosolic fraction, reaching a maximum (twofold) after 15 min. Incubation of adrenal ZF with 8Br-cAMP also produced PTP activation, suggesting that it can be mediated by cAMP-dependent protein kinase (PKA)-dependent phosphorylation. Detection of PTP activity in an in-gel assay showed three corticotropin-stimulated soluble PTPs with molecular masses of 115, 80 and 50 kDa. In summary, we report for the first time a hormone-dependent PTP activation in a steroidogenic tissue and provide evidence that PTP activity plays an important role in corticotropin signal pathway, acting downstream of PKA activation and upstream of cholesterol transport across the mitochondrial membrane.
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PMID:Corticotropin increases protein tyrosine phosphatase activity by a cAMP-dependent mechanism in rat adrenal gland. 1051 84


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