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 functional recovery from impaired motor activity caused by 6-OHDA lesions in the nucleus accumbens is accelerated by the ACTH-related peptides ACTH-(4-10), alpha-MSH (ac-Ser1-ACTH-(1-13)NH2), ACTH-(7-10) and the ACTH-(4-9) analog ORG 2766. The peptides ACTH-(4-7) and Phe-D-Lys-Phe were not effective in this respect. This indicates that this effect of ACTH-derived peptides is located in the 7-10 part of the molecule whereas for the effect of ORG 2766 a bigger part of the molecule may be required. ORG 2766 was effective after intra-accumbal, subcutaneous and oral administration. The differences in potencies between the 3 routes of administration (ED50 0.76 ng/kg, 28.5 ng/kg and 80.6 micrograms/kg, respectively) suggest that the peptide exerts its effect by facilitating recovery processes at the lesion site. Studies with ORG 2766 showed that treatment during the first days following the induction of the lesion is essential for the facilitating action of the peptide on spontaneous recovery from brain damage.
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PMID:Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. III. Further analysis of the facilitating effect of the ACTH-(4-9) analog ORG 2766. 215 94

In a modified Krebs buffer at 37 degrees C, the selective mu agonist [3H] D-Ala2,MePhe4,Gly-ol5]enkephalin [( 3H]DAMGO) and the nonselective mu/delta agonist human [125I]beta-endorphin [( 125I]beta-endH) bound to rat striatal membranes with a Kd of about 7 and 5 nM and a Bmax of about 95 and 260 fmol/mg of protein, respectively, consistent with labeling of mu receptors by the former ligand and labeling of both mu and delta receptors by the latter. The binding of 2 nM [125I]beta-endH was displaced by unlabeled DAMGO (IC50 30 nM), [D-Ala2-D-Leu5]enkephalin (IC50 60 nM) as well as by the selective delta agonists [D-Ser2(O-tert-butyl),Leu5]enkephalyl-Thr6 (DSTBULET, IC50 500 nM) and Tyr-Ala-Phe-Asp-Val-Val-Gly-NH2 (IC50 700 nM) in a monophasic manner within 2 to 3 log concentration units, suggesting an allosteric interaction between mu and delta sites labeled by [125I]beta-endH under these conditions. Accordingly, 500 nM DSTBULET caused almost 40% inhibition of the apparent Bmax without changing the apparent Kd of [3H] DAMGO. The kappa agonist U 50,488 was ineffective as competing ligand even at a concentration of 10 microM. Upon affinity cross-linking of [125I]beta-endH (2 nM) to rat striatal mu- and delta-opioid receptors, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the solubilized tissue under reducing conditions followed by autoradiography of the dried gels revealed a major broad band of covalently labeled protein with an apparent molecular weight of 80 kDa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cross-linking of human [125I]beta-endorphin to opioid receptors in rat striatal membranes: biochemical evidence for the existence of a mu/delta opioid receptor complex. 215 52

Dermorphin, Tyr-DAla-Phe-Gly-Tyr-Pro-Ser-NH2, a potent opioid peptide isolated from amphibian skin, is endowed with outstanding structural and biological features. It has no common structure with mammalian opioid peptides and is a unique example of a peptide, synthesized by an animal cell, which contains a D-amino acid in its native sequence. We have undertaken a complete evaluation of the receptor selectivity of dermorphin, together with the binding characteristics and receptor distribution of [3H]dermorphin in the rat brain. 1. Dermorphin was tested for its relative affinity to mu-, delta- and chi-opioid receptors by determining its potency in displacing the selective mu-receptor ligand [3H]Tyr-DAla-Gly-MePhe-Gly-ol (where Gly-ol = glycinol), the prototypic delta-receptor ligand [3H]Tyr-DPen-Gly-Phe-DPen (where DPen = beta, beta-dimethylcysteine) and the chi ligand [3H]ethylketocyclazocine from rat brain and/or guinea pig cerebellum membrane preparations. Inhibitory constant (Ki) values of dermorphin were 0.7 nM, 62 nM and greater than 5000 nM respectively for mu, delta and chi sites, indicating a selectivity ratio Ki(delta)/Ki(mu) = 88. Under similar conditions, Tyr-DAla-Gly-MePhe-Gly-ol, which is regarded as one of the most selective high-affinity mu-agonist available, exhibited a selectivity ratio of 84. 2. Specific binding properties of tritium-labeled dermorphin (52 Ci/mmol) were characterized in the rat brain. Equilibrium measurements performed over a large range of concentrations revealed a single homogeneous population of high-affinity binding sites (Kd = 0.46 nM; Bmax = 92 fmol/mg membrane protein). 3. Profound differences were observed in the potencies displayed by various selective opiates and opioids ligands in inhibiting the specific binding of [3H]dermorphin. The rank order of potency was in good agreement with that obtained with other mu-selective radiolabeled ligands. 4. Receptor autoradiography in vitro was used to visualize the distribution of [3H]dermorphin binding sites in rat brain. The labeling pattern paralleled that observed using other mu probes. Binding parameters and selectivity profile of [3H]dermorphin on slide-mounted sections were similar to those obtained with membrane homogenates. 5. Finally, intracerebroventricular administration of synthetic dermorphin into mice showed that this peptide is the most potent analgesic known to date, being up to 5 and 670 times more active than beta-endorphin and morphine, respectively. Higher doses induced catalepsy. The overall data collected demonstrate that dermorphin is the first among the naturally occurring peptides to be highly potent and nearly specific super-agonist towards the morphine (mu) receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterisation and visualisation of [3H]dermorphin binding to mu opioid receptors in the rat brain. Combined high selectivity and affinity in a natural peptide agonist for the morphine (mu) receptor. 216 61

Based on structure-activity relationships of the potent alpha-MSH agonist, Ac-Nle4-Asp5-His6-D-Phe7-Arg8-Trp9-Lys10-NH2, several analogs of the general formula Ac-Nle4-Asp5-Waa6-Xaa7-Yaa8-Zaa9-Lys10+ ++-NH2 were synthesized and tested on frog and lizard skin bioassays for their possible inhibitory actions against alpha-MSH on melanocyte stimulation. When Waa6 = Trp, Xaa7 = D-Phe, Yaa8 = Nle and Zaa = Trp, a highly potent alpha-MSH antagonist, Ac-Nle-Asp-Trp-D-Phe-Nle-Trp-Lys-NH2, with selectivity on the frog skin alpha-MSH receptor system (pA2 = 8.4) was obtained. However, several modifications in the amino acid sequence of the peptide resulted in a complete loss of antagonistic activity and a recovery of very weak agonistic action. The following changes in the amino acid sequence of the peptide were examined; His or D-Trp for Waa, L-Phe for Xaa, Arg, Ala or Pro for Yaa, and D-Trp for Zaa. All resulted in full agonists with no antagonistic activity. In addition, lactam cyclization between the Asp5 and Lys10 side chains in the antagonist gave a full agonist and a complete loss of antagonistic activity. Efforts to develop a rational approach for the design of selective alpha-MSH antagonists for the frog skin alpha-MSH receptor will be discussed.
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PMID:Design, synthesis, and biological activities of a potent and selective alpha-melanotropin antagonist. 216 30

The present studies were designed to determine what type of opioid receptor, mu or delta, in the spinal cord was involved in beta-endorphin-induced antinociception. The tail-flick response was used as an antinociceptive test. Intrathecal (i.t.) injection of ICI-174,864 [(Allyl)2-Tyr-Aib-Aib-Phe-Leu-OH] (10 micrograms) or ICI-154,129 [(N,N-Bisallyl)-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH] (20 micrograms), delta-opioid receptor antagonists, but not beta-funaltrexamine (0.025 microgram), a mu-opioid receptor antagonist, antagonized inhibition of the tail-flick response induced by beta-endorphin given i.c.v. However, i.t. injection of the same dose of ICI-174,864, ICI-154,129 or beta-funaltrexamine did not affect inhibition of the tail-flick response induced by morphine given i.c.v. Mice were pretreated i.c.v. with either beta-endorphin (2 micrograms), morphine (2 micrograms) or saline (5 microliters) for 2, 3 or 4 hr (which were times that the tail-flick response was no longer inhibited) and were injected i.t. with various doses of D-Ala2-NMePhe4-Gly-ol-enkephalin (a selective mu-opioid receptor agonist), D-Ala2-D-Leu5-enkephalin (a mu- and delta-opioid receptor agonist) or D-Pen2-D-Pen5-enkephalin (a delta-opioid receptor agonists). The tail-flick response was performed 10 min after i.t. injection. A single i.c.v. pretreatment with beta-endorphin for 2 and 3 hr, but not 4 hr, reduced markedly the inhibition of the tail-flick response induced by D-Pen2-D-Pen5-enkephalin and D-Ala2-DLeu5-enkephalin, but not D-Ala2-NMePhe4-Gly-ol-enkephalin, injected i.t.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Delta but not mu-opioid receptors in the spinal cord are involved in antinociception induced by beta-endorphin given intracerebroventricularly in mice. 216 54

D-Tyr-Ser-Gly-Phe-Leu-Thr (DSLET), beta-endorphin, morphiceptin and morphine were microinjected at 48-h intervals into the amygdala or hippocampus of awake rats in an attempt to identify the opiate receptor types involved in opioid kindling. DSLET, beta-endorphin, morphiceptin and morphine were injected into the lateral ventricle to assess the possibility of kindling seizures by this route. The delta-receptor agonist DSLET effectively kindled convulsions when microinjected into amygdala or ventral hippocampus. The convulsions were suppressed or strongly attenuated by ICI 174,864, a specific antagonist of the delta-receptor, microinjected into the same brain site, but were not affected by ICI 174,864 administered peripherally. When microinjected into amygdala or hippocampus, beta-endorphin and morphiceptin also kindled convulsions, which were antagonized by naloxone but not by ICI 174,864. Morphine evoked EEG epileptiform activity but did not kindle convulsions from limbic brain sites. DSLET occasionally evoked epileptiform spiking and submaximal convulsions when injected into ventricle, and morphiceptin evoked epileptiform spiking only, but tolerance to these effects occurred after repetition of the injections. Thus, convulsions can be kindled by activation of either mu-, delta- or epsilon-receptors when opioids are injected directly into limbic tissue. However, the ability of these compounds to kindle seizures is markedly reduced when they are administered into ventricle. The striking differences between the present results and previous results obtained by peripheral or intraventricular administration of opioid peptides suggest that the route of administration, among other variables, is a crucial factor in assessing the epileptogenic properties of opioid peptides.
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PMID:Involvement of multiple opiate receptors in opioid kindling. 216 33

1. The plasma levels of L-tryptophan (L-TRP) and the sum of five competing amino acids (CAA) namely tyrosine, phenylalanine, valine, leucine, isoleucine, were determined in 79 depressed females categorized according to the DSM-III. 2. In these patients the authors measured several parameters known to affect the availability of the above amino acids, i.e. triidothyronine (FT3) and thyroxine (FT4), vanilylmandelic acid (VMA), noradrenaline and adrenaline in 24 hr urine, the sex hormonal and nutritional state. 3. The 1 mg dexamethasone suppression test was performed and the pre and postdexamethasone cortisol and adrenocorticotropic hormone (ACTH) levels were determined at 8 a.m. 4. L-TRP and the ratio L-TRP/CAA were significantly lower in severely depressed females (296.X3, 296.X4) as compared with minor (300.40, 309.00) and simple major depressives (296.X2). The ratio L-TRP/CAA performed well as a clinical tool separating melancholic from minor depression. 5. FT3, FT4, VMA and noradrenaline were significantly increased in the severely depressed females, but these data did not correlate with the availability of L-TRP. Neither baseline cortisol nor the sex hormonal, nor the nutritional state related to the L-TRP data. The ratio L-TRP/CAA was significantly and negatively correlated with the postdexamethasone cortisol and ACTH values.
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PMID:The decreased availability of L-tryptophan in depressed females: clinical and biological correlates. 217 60

For chemical affinity labeling of the melanotropin receptor several alpha-MSH fragments containing phenylalanine mustard were synthesized in solution. Tested in the frog skin bioassay the derivatives roughly preserved the biological activity of the corresponding natural sequences. Alkylating peptides with prolonged biological activity containing phenylalanine mustard in place of arginine, phenylalanine or methionine are inhibitors of alpha melanotropin, suggesting an irreversible binding to reactive nucleophiles on the part of the MSH receptor, where the Met-Glu-His-Phe-Arg sequence is attached.
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PMID:Synthesis of alpha-MSH fragments containing phenylalanine mustard for receptor studies. 217 34

We have constructed a vast library of peptides for finding compounds that bind to antibodies and other receptors. Millions of different hexapeptides were expressed at the N terminus of the adsorption protein (pIII) of fd phage. The vector fAFF1, derived from the tetracycline resistance-transducing vector fd-tet, allows cloning of oligonucleotides in a variety of locations in the 5' region of gene III. A library of 3 x 10(8) recombinants was generated by cloning randomly synthesized oligonucleotides. The library was screened for high-avidity binding to a monoclonal antibody (3-E7) that is specific for the N terminus of beta-endorphin (Tyr-Gly-Gly-Phe). Fifty-one clones selected by three rounds of the affinity purification technique called panning were sequenced and found to differ from previously known ligands for this antibody. The striking finding is that all 51 contained tyrosine as the N-terminal residue and that 48 contained glycine as the second residue. The binding affinities of six chemically synthesized hexapeptides from this set range from 0.35 microM (Tyr-Gly-Phe-Trp-Gly-Met) to 8.3 microM (Tyr-Ala-Gly-Phe-Ala-Gln), compared with 7.1 nM for a known high-affinity ligand (Tyr-Gly-Gly-Phe-Leu). These results show that ligands can be identified with no prior information concerning antibody specificity. Peptide libraries are also likely to be useful in finding ligands that bind to other classes of receptors and in discovering pharmacologic agents.
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PMID:Peptides on phage: a vast library of peptides for identifying ligands. 220 Oct 29

1. An immunoassay technique employing an enzyme-labelled ligand was developed for the sulfoxide derivative of the opioid peptide methionine-enkephalin (MOE). 2. The sensitivity of the enzyme immunoassay (EIA) was approximately twofold higher than that achieved in the radio-immunoassay (RIA) using tritiated ligand. Cross-reactivities of leucine-enkephalin and beta-endorphin with the EIA were less than 0.1%, while that with Gly-Gly-Phe-Met and oxidized Gly-Gly-Phe-Met were 2.5% and 10.2%, respectively. 3. These results indicate that the EIA is a useful alternative to the RIA for the assay of small peptides.
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PMID:Enzyme immunoassay for methionine-enkephalin sulfoxide. 220 25


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