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)

Adrenocorticotropic (ACTH) and melanocyte stimulating (MSH) hormones have been demonstrated in the same cells in the cephalic half of the pars distalis of the chicken pituitary glands in three ways: (I) immunohistochemistry, (II) radioimmunoassay (RIA) using both anti-human or porcine ACTH and synthetic alpha-MSH antibodies, and (III) isolation and purification, followed by the determination of amino acid compositions of both hormones. The contents of ACTH and alpha-MSH are estimated by RIA to be 1600 and 10 ng/gland, respectively. ACTH missed 1 (des-Phe39-ACTH) or 2 residues (des-Glu38, Phe39-ACTH) from the C-terminal portion was also isolated. The recoveries of these ACTHs are differed from preparation to preparation. The complete amino acid sequence of chicken ACTH (39 residues) has been determined as NH2-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-Gly-Arg-Lys-Arg- Arg- Pro-Ile-Lys-Val-Tyr-Pro-Asn-Gly-Val-Asp-Glu-Glu-Ser-Ala-Glu-Ser-Tyr-Pro- Met-Glu-Phe-OH Strikingly the amino acid sequence of chicken ACTH shows a closer resemblance to that from an amphibian, Xenopus (3 residue substitution) than that from another bird, the ostrich (7 residue substitution) or the turkey (at least 9 residue substitution).
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PMID:Characterization of chicken ACTH and alpha-MSH: the primary sequence of chicken ACTH is more similar to Xenopus ACTH than to other avian ACTH. 165 32

The composition and blood concentration of free aminoacids and other aminocompounds were investigated using automatic aminoacid analysis by a physiological program in 12 patients with diagnosed corticotropin secreting hypophyseal disease (Itsenko-Cushing disease) before and 1-3 years after proton "hypophysectomy". Imbalance of components of the glucose-alanine cycle, expressed in hypoalaninemia and raised concentration of aminoacids with a bifurcated lateral chain, was detected against a background of marked hypercorticotropinemia and hypercorticolism. Single irradiation of the pituitary gland with a proton beam at absorbed doses of 100-120 Gy in the maximum of a deep field resulted in remission and normalization of aminograms of blood plasma (suggesting pathogenicity of proton-beam therapy) for 6-12 mos. The authors discussed probable mechanisms of the interrelationship of protein-amino-acid and carbohydrate metabolic derangements and their correlation with a type of changes in the hormonal balance.
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PMID:[The effect of proton therapy on the protein-amino acid metabolism in Itsenko-Cushing disease]. 165 73

The guinea-pig has high levels of circulating cortisol. Though adrenocorticotropin (ACTH) levels are similar to those in other mammals, guinea-pig ACTH has been reported to have a single amino-acid substitution which results in increased bioactivity of the peptide. Pro-opiomelanocortin (POMC) is the precursor for ACTH, gamma-melanocyte-stimulating hormone (gamma-MSH) and the endogenous opioid peptide beta-endorphin. Both to confirm this substitution in guinea-pig ACTH and to establish whether other non-conservative substitutions occur elsewhere in the precursor we cloned guinea-pig POMC. The guinea-pig alanine for proline substitution at position 24 of ACTH was confirmed. Potentially significant mutations were also identified in gamma-MSH and beta-endorphin. A similar pattern of POMC mRNA expression was obtained for guinea-pig and rat as determined by Northern analysis and in situ hybridization. Southern blot analysis indicated that guinea-pig POMC is a single-copy gene. Cloning and sequencing of guinea-pig POMC thus further demonstrate the divergence of the New World hystricomorph peptides from those in New World primates, and underscore the differences observed in other endocrine axes in the guinea-pig.
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PMID:Molecular cloning and sequencing of a guinea-pig pro-opiomelanocortin cDNA. 166 66

The duration of action and potency of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidases 24.11 and 24.15. Whereas endopeptidase 24.11 cleaves enkephalin pentapeptides, endopeptidase 24.15 degrades longer-chained opioids including dynorphin A1-8 and met-enkephalin-Arg6-Gly7-Leu8 (MERGL). Inhibitors of endopeptidase 24.11 and 24.15 both increase basal nociceptive thresholds and respective forms of opioid antinociception. Acute exposure to certain environmental stressors can produce antinociception which is opioid mediated; inhibitors of endopeptidase 24.11 potentiate this effect. The present study evaluated whether central administration of a selective inhibitor of endopeptidase 24.15, N-[1-(RS)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-p-aminobenzoate (cFP-AAF-pAB) increased antinociception following intermittent cold-water swims (ICWS) in rats. cFP-AAF-pAB (0.25-25 nmol, ICV) dose-dependently increased ICWS antinociception on the tail-flick and jump tests without affecting basal nociceptive thresholds. The opioid mediation of ICWS antinociception was confirmed by significant reductions in this response following naloxone. These data indicate that longer-chained endogenous opioid peptides participate in the antinociception induced by ICWS.
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PMID:Increases in opioid-mediated swim antinociception following endopeptidase 24.15 inhibition. 166 30

Intermediate pituitaries of the reptile, Anolis carolinensis, were separately pulse labeled with [3H]Trp and [3H]Tyr. The major form of alpha-MSH was purified by immunoprecipitation and isolated by reverse phase HPLC. Tryptic peptide analysis indicated that the [3H]Trp-labeled C-terminal fragment of Anolis alpha-MSH had the same retention time as mammalian ACTH(9-13) amide; however, the [3H]Tyr-labeled N-terminal fragment did not coelute with either mammalian ACTH(1-8) or N-acetyl-ACTH(1-8). Purification of alpha-MSH from 76 Anolis intermediate pituitaries confirmed that a sequence change had occurred in the N-terminal region of Anolis alpha-MSH. The tissues were acid extracted and purified by Sephadex G-25 chromatography and reverse phase HPLC to yield 4.5 micrograms of purified Anolis alpha-MSH for amino acid composition analysis and automated Edman degradation sequence analysis. The major form of Anolis alpha-MSH is nonacetylated and has the following novel primary sequence: Ser-Tyr-Ala-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro(Val-amide). The presence of Val-amide was verified by immunological analysis, tryptic peptide analysis and amino acid composition analysis.
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PMID:Detection of a novel sequence change in the major form of alpha-MSH isolated from the intermediate pituitary of the reptile, Anolis carolinensis. 166 89

The substrate specificity of polysome rat liver N alpha-acetyltransferase (NAT) has been examined by utilizing a series of synthetic and natural substrates that has been systematically altered with respect to N-terminal sequence and length. Families of peptides of the structure S-Y-S-G-G-L-L-L were generated by successively replacing the N-terminal serine, the penultimate tyrosine, and the antepenultimate serine with all 19 commonly occurring amino acids, which were then assessed for their reactivity with the rat liver enzyme. Only peptides with N-terminal serine, alanine, methionine, leucine, and phenylalanine were modified. Glycine, lysine, arginine, valine, isoleucine, and tryptophan in the second position are (with N-terminal serine) strongly inhibitory, and proline completely blocks modification. Third-position substitutions have less of an effect on NAT activity with glycine, aspartic acid, glutamic acid, and tryptophan being most inhibiting (with N-terminal Ser-Tyr). These observations are generally in agreement with in situ modifications although there are some significant differences particularly with respect to the amino-terminal residues. Optimal chain length was determined to be 10-11 residues with either synthetic peptides of the structure S-Y-S-(G)n-L-L-L or adrenocorticotropin (ACTH) sequences ranging from 8 to 39 residues. The ACTH peptides were generally found to be severalfold better substrates than the corresponding synthetic ones. Activity was not affected by increased chain length beyond approximately 17 residues. These data support the view that polysome-catalyzed N alpha-acetylation occurs as a cotranslational event on nascent chains of about 20-40 amino acids in length.
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PMID:Rat liver polysome N alpha-acetyltransferase: substrate specificity. 184 56

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

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

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

The neuropeptides neurotensin, substance P, neurokinin-alpha (substance K), and met-enkephalin are present endogenously in the ventral tegmental area (VTA), site of the A10 dopaminergic (DA) cell bodies. In the present study these four peptides were injected bilaterally into the VTA in the rat, and the effects on operant behavior were assessed. Cannulae aimed at the VTA were implanted in four groups of animals, which had been trained to bar-press for food reward on a fixed-interval, 40-s schedule. A fifth group, in which the effects of systemically administered amphetamine were assessed, was also tested. Response rate across the interval was measured, and the index of quarter-life was taken as an indication of the temporal pattern of responding. In addition, a rate-dependency analysis was carried out for all data. Neurotensin (NT, 0.0175, 0.175, 0.5 micrograms in 1 microliter) dose-dependently decreased response rates without affecting quarter-life, and reduced the number of reinforcements obtained. Substance P (SP, 0.1, 1.0, 3.0 micrograms) did not affect responding, and neurokinin-alpha (NKA, 0.1, 1.0, 3.0 micrograms) induced a small increase in responding. Quarter-life was not affected by SP or NKA, but responding on the non-reinforced lever was significantly increased by both peptides. d-Ala-met-enkephalin (DALA, 0.01, 0.1, 1.0 micrograms) induced a dose-dependent increase in responding which was also rate-dependent, and reduced quarter-life. DALA effects were similar to the classic pattern of responding observed after systemic amphetamine. These results suggest that although all these peptides elicit behavioral activation and may affect DA neuronal activity, the behavioral responses can be differentiated with respect to operant behavior.
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PMID:Neurotensin, substance P, neurokinin-alpha, and enkephalin: injection into ventral tegmental area in the rat produces differential effects on operant responding. 247 Dec 21


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