110 results on '"beta-Endorphin analogs & derivatives"'
Search Results
102. Synaptosomal membrane-bound form of endopeptidase-24.15 generates Leu-enkephalin from dynorphin1-8, alpha- and beta-neoendorphin, and Met-enkephalin from Met-enkephalin-Arg6-Gly7-Leu8.
- Author
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Acker GR, Molineaux C, and Orlowski M
- Subjects
- Animals, Chromatography, High Pressure Liquid, Dynorphins metabolism, Endorphins metabolism, Enkephalin, Methionine analogs & derivatives, Male, Peptide Fragments metabolism, Protease Inhibitors, Protein Precursors metabolism, Rats, Rats, Inbred Strains, Synaptic Membranes enzymology, Trypsin metabolism, Brain enzymology, Endopeptidases metabolism, Enkephalin, Leucine metabolism, Enkephalin, Methionine metabolism, Metalloendopeptidases, Synaptosomes enzymology, beta-Endorphin analogs & derivatives
- Abstract
Brain contains a membrane-bound form of endopeptidase-24.15, a metalloendopeptidase predominantly associated with the soluble protein fraction of brain homogenates. Subcellular fractionation of the enzyme in rat brain showed that 20-25% of the total activity is associated with membrane fractions including synaptosomes. Solubilization of the enzyme from synaptosomal membranes required the use of detergents or treatment with trypsin. The specific activity of the enzyme in synaptosomal membranes measured with tertiary-butoxycarbonyl-Phe-Ala-Ala-Phe-p-aminobenzoate as substrate was higher than that of endopeptidase-24.11 ("enkephalinase"), a membrane-bound zinc-metalloendopeptidase believed to function in brain neuropeptide metabolism. Purified synaptosomal membranes converted efficiently dynorphin1-8, alpha- and beta-neoendorphin into leucine enkephalin and methionine-enkephalin-Arg6-Gly7-Leu8 into methionine enkephalin in the presence of captopril, bestatin, and N-[1-(R,S)-carboxy-2-phenylethyl]-Phe-p-aminobenzoate, inhibitors of angiotensin converting enzyme (EC 3.4.15.1), aminopeptidase (EC 3.4.11.2), and membrane-bound metalloendopeptidase (EC 3.4.24.11), respectively. The conversion of enkephalin-containing peptides into enkephalins was virtually completely inhibited by N-[1-(R,S)-carboxy-2-phenylethyl]-Ala-Ala-Phe-p-aminobenzoate, a specific active-site-directed inhibitor of endopeptidase-24.15, indicating that this enzyme was responsible for the observed interconversions. The data indicate that synaptosomal membranes contain enzymes that can potentially generate and degrade both leucine- and methionine-enkephalin.
- Published
- 1987
- Full Text
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103. Differential effects of beta-endorphin fragments on human natural killing.
- Author
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Williamson SA, Knight RA, Lightman SL, and Hobbs JR
- Subjects
- Cytotoxicity, Immunologic drug effects, Dipeptides pharmacology, Endorphins pharmacology, Humans, In Vitro Techniques, Killer Cells, Natural immunology, Structure-Activity Relationship, alpha-Endorphin, beta-Endorphin analogs & derivatives, Killer Cells, Natural drug effects, Peptide Fragments pharmacology, beta-Endorphin pharmacology
- Abstract
The endogenous opiate peptide, beta-endorphin, has two effects on human natural killing (NK). Preincubation of effector lymphocytes with between 10(-7) and 10(-11) M beta-endorphin increases NK. Preincubation with lower concentrations results in a reduction in NK. Endorphin peptides containing an unmodified N-terminal sequence, and which are known to bind only to opiate receptors, increase NK. Sequences reported to bind only to nonopiate receptors reduce NK.
- Published
- 1987
- Full Text
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104. On the origin of Leu-enkephalin and Met-enkephalin in the rat neurohypophysis.
- Author
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Zamir N
- Subjects
- Animals, Arginine Vasopressin analysis, Dynorphins analogs & derivatives, Dynorphins analysis, Endorphins analysis, Hypothalamus, Middle metabolism, Male, Paraventricular Hypothalamic Nucleus analysis, Peptide Fragments analysis, Protein Precursors analysis, Rats, Rats, Inbred Strains, Rats, Inbred WKY, Sodium Glutamate pharmacology, Enkephalin, Leucine biosynthesis, Enkephalin, Methionine biosynthesis, Pituitary Gland, Posterior metabolism, beta-Endorphin analogs & derivatives
- Abstract
The posterior lobe of the pituitary contains large amounts of Leu- and Met-enkephalin (LE and ME, respectively). A marked depletion of ME (81.9%) and LE (94.5%) in the posterior pituitary occurred after transection of the pituitary stalk. This indicates that most, if not all, of the enkephalins are in processes of central neurons. In the present study, I attempted to determine the source(s) of the LE- and ME-containing fibers in the posterior pituitary by examining the effects of hypothalamic lesions or fiber transections on the LE and ME levels. Lesions of the hypothalamic paraventricular nuclei caused ME and LE levels in the posterior pituitary to decrease significantly (55.6% and 27.6%, respectively). Deafferentation of the medial basal hypothalamus (creating islands of tissue containing the ventromedial and arcuate nuclei) resulted in a marked reduction in LE (94.1%) and ME (54.7%). Treating neonatal rats with monosodium glutamate resulted in a selective destruction of arcuate nucleus neurons, but did not affect LE and ME concentrations in the posterior pituitary. Thus, about half of the ME in the posterior pituitary seems to be provided by neurons in the vicinity of the paraventricular and ventromedial nuclei, whereas only about one quarter of the LE in the posterior pituitary is in processes of the paraventricular nucleus neurons. The remainder of the LE is contributed to the posterior pituitary by neurons outside the medial basal hypothalamus, probably by the supraoptic nucleus neurons. These findings are consistent with the hypothesis that LE and ME may be localized in separate populations of nerve endings in the neurohypophysis and may have different roles.
- Published
- 1985
- Full Text
- View/download PDF
105. N alpha-acetyl-beta-endorphin stimulates ornithine decarboxylase activity in preweanling rat pups: opioid- and non-opioid-mediated mechanisms.
- Author
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Bartolome JV, Bartolome MB, Harris EB, and Schanberg SM
- Subjects
- Aging, Animals, Brain enzymology, Kinetics, Rats, Rats, Inbred Strains, Tissue Distribution, Brain growth & development, Endorphins pharmacology, Ornithine Decarboxylase metabolism, beta-Endorphin analogs & derivatives
- Abstract
Our laboratory has demonstrated recently that administration of beta-endorphin to rat pups results in profound changes in the levels of the growth-related enzyme ornithine decarboxylase (ODC) in both brain and peripheral tissues. These findings are consistent with accumulated evidence indicating that, in addition to their analgesic and behavioral effects in the adult, endogenous opioid peptides and opioid receptors may be involved as mediators of tissue growth and function in the neonate. This study examines the effects of N alpha-acetyl-beta-endorphin on tissue ODC activity to determine whether post-translational acetylation of beta-endorphin at the N alpha-terminus affects its capability to alter ODC activity and, consequently, tissue development. Intracisternal administration of N alpha-acetyl-beta-endorphin evoked profound increases in brain ODC activity in 6- and 9-day-old rats, whereas normal ODC levels were observed in 25-day-old animals and in adult rats. Centrally administered N alpha-acetyl-beta-endorphin had no effect on ODC in peripheral tissues. In contrast, s.c. administration of this peptide to 6-day-old animals resulted in marked increases in ODC activity in the heart, liver and brain. Naloxone inhibited the stimulatory actions of N alpha-acetyl-beta-endorphin on brain ODC completely, indicating the involvement of opioid receptors in that process. On the other hand, the increases in liver ODC were not prevented by naloxone, suggesting that these effects are not mediated through opioid-sensitive structures.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1987
106. Biotinylated human beta-endorphins as probes for the opioid receptor.
- Author
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Hochhaus G, Gibson BW, and Sadée W
- Subjects
- Animals, Binding, Competitive, Biotin metabolism, Cell Line, Glioma, Humans, Hybrid Cells metabolism, Kinetics, Neuroblastoma, Structure-Activity Relationship, Receptors, Opioid metabolism, beta-Endorphin analogs & derivatives, beta-Endorphin metabolism
- Abstract
The reaction of human beta-endorphin and biotinyl N-hydroxysuccinimide with or without spacer arm, afforded a series of products that were separated by high performance liquid chromatography (HPLC). Liquid secondary ion mass spectrometry of the biotinylated products and their tryptic digests produced abundant protonated molecular ions (MH+), which specified the number and location of biotinylation. Between 1 and 4 biotinyl residues were incorporated per human beta-endorphin molecule, at Lys-9, -19, -24, -28, and -29, but not at the amino-terminal Tyr-1. Three HPLC fractions were isolated for receptor binding studies with monobiotinylation of Lys-9 (B1 beta and B1X beta; X = C6 spacer arm), Lys-19 (B1 gamma), and a mixture of Lys-24, Lys-28, and Lys-29 derivatives (B1 alpha, BX1 alpha). All derivatives displayed tight binding to avidin, and no dissociation from avidin was detectable over several hours at 0 degrees C for the derivatives (BX1 alpha) tested. IC50 values for binding to mu and delta opioid receptor sites were 3-8 times higher for monobiotinylated derivatives than for the parent human beta-endorphin (IC50,mu = 1.5 nM, IC50,delta = 1.3 nM). Association with avidin decreased opioid receptor affinities for the C6 spacer derivative biotinylated at position Lys-9, which is close to the (1-5) enkephalin receptor region. In contrast, avidin did not affect or even increased apparent affinities to mu and delta sites for derivatives biotinylated at the alpha-helical part of the molecule (Lys-19, -24, -28, and -29). Thus, when bound to avidin, the biotinylated human beta-endorphin derivatives with spacer arm (BX1 alpha), substituted near the carboxyl terminal (Lys-24, -28, and -29), displayed mu binding affinities equal to and delta binding affinities only four times lower than underivatized human beta-endorphin. Biotinylated human beta-endorphins also bound to low affinity nonopioid binding sites on NG-108-15 cells; however, affinities to these sites were considerably reduced when derivatives were bound to avidin. The ability of biotinylated human beta-endorphin to cross-link the mu and delta opioid receptors to avidin allows application of the biotin-avidin system as a molecular probe of the opioid receptor.
- Published
- 1988
107. Non-opiate effects of neuropeptides derived from beta-endorphin.
- Author
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De Wied D and Van Ree JM
- Subjects
- Animals, Brain drug effects, Brain physiology, Neuropeptides pharmacology, Peptide Fragments pharmacology, beta-Endorphin analogs & derivatives, beta-Endorphin pharmacology
- Abstract
Brain enzymes convert the opioid peptide beta-endorphin (beta E-(1-31)) to alpha- and gamma-endorphin and to several non-opioid fragments by further cleavage of the tyrosine residue or acetylation. Several of these peptides selectively affect brain functions. alpha-Endorphin (beta E-(1-16)) and relate non-opioid fragments (beta E-(2-16), beta E-(2-9) a.o.) like amphetamine, delay extinction of pole-jumping avoidance behavior and facilitate passive avoidance behavior. In addition these peptides enhance the stereotyped sniffing response induced by the injection of apomorphine into the nucleus caudatus. The fragment beta E-(10-16) inhibits, like serotonin and antidepressants, the behavioral effects of melatonin injected into the nucleus accumbens. gamma-Endorphin (beta E-(1-17)) has inherent opioid and neuroleptic-like properties, e.g. demonstrated by a naloxone reversible inhibition of hypermotility induced by apomorphine following injection into the nucleus accumbens. Also the non-opioid gamma-type endorphins (e.g. DT gamma E (beta E-(2-17) and DE gamma E (beta E-(6-17)) mimic certain effects of neuroleptics. These peptides facilitate extinction of pole-jumping avoidance behavior, attenuate passive avoidance behavior and antagonize the hypomotility and stereotyped sniffing induced by apomorphine injected into the nucleus accumbens and pyriform cortex respectively. These and other behavioral studies, including grasping responses, brain stimulation reward, food and other positively rewarded behavior, indicate that the action of alpha-type endorphins is in some aspects comparable to that of psychostimulants, while the effects of gamma-type endorphins are comparable to those of classical as well as atypical neuroleptics. Indeed, gamma-type endorphins have antipsychotic effects in a category of schizophrenic patients.
- Published
- 1987
108. POMC in rhesus anterior pituitary and plasma: evidence of N-acetylated beta-endorphin and alpha-MSH.
- Author
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Cahill C, Watson SJ, Knobloch M, and Akil H
- Subjects
- Animals, Macaca mulatta, Melanocyte-Stimulating Hormones analysis, Pituitary Hormones, Anterior blood, Pro-Opiomelanocortin, Protein Precursors blood, Radioimmunoassay, Endorphins analysis, Melanocyte-Stimulating Hormones analogs & derivatives, Pituitary Gland, Anterior analysis, Pituitary Hormones, Anterior analysis, Protein Precursors analysis, alpha-MSH analogs & derivatives, beta-Endorphin analogs & derivatives
- Abstract
Pro-opiomelanocortin (POMC) related peptides have been studied in rat tissue and plasma, but they have not been well characterized in the rhesus monkey. Since monkey pituitary may be more similar to the human pituitary than the rat, we have characterized POMC related peptides by immunocytochemical, multiple radioimmunoassays (RIA's) and molecular sieving chromatography. Immunocytochemical staining demonstrated N-acetylated- beta-endorphin (N-Ac- beta-End) and alpha-MSH in a few corticotrophs. RIA's of crude anterior pituitary extract and molecular sieving chromatography demonstrates that the major portion is beta-End sized with a significant proportion being N-acetylated and an alpha-MSH peak. Molecular sieving chromatography of extracted plasma demonstrated a similar pattern to that seen in the anterior pituitary. These data suggest that rhesus monkey processes POMC differently than rat or man.
- Published
- 1983
- Full Text
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109. Effects of dehydration on pro-dynorphin derived peptides in the neuro-intermediate lobe of the rat pituitary.
- Author
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Lorenz RG, Evans CJ, and Barchas JD
- Subjects
- Animals, Dynorphins metabolism, Endorphins metabolism, Enkephalin, Leucine metabolism, Food Deprivation, Hypothalamus metabolism, Male, Peptide Fragments metabolism, Rats, Rats, Inbred Strains, Dehydration metabolism, Enkephalins metabolism, Pituitary Gland, Posterior metabolism, Protein Precursors metabolism, beta-Endorphin analogs & derivatives
- Abstract
Dehydration significantly reduced the concentration of immunoreactive dynorphin A(1-17), dynorphin A(1-8), alpha-neo-endorphin, beta-neo-endorphin, and leu-enkephalin in the rat pituitary posterior-intermediate lobe. A statistically significant increase in immunoreactive dynorphin A(1-8), alpha-neo-endorphin and leu-enkephalin was observed in the hypothalamus. Comparison of the molar ratios of dynorphin A(1-17): dynorphin A(1-8) and alpha-neo-endorphin: beta-neo-endorphin showed an altered profile of stored pro-dynorphin cleavage products in the posterior-intermediate lobe of the pituitary of dehydrated rats.
- Published
- 1985
- Full Text
- View/download PDF
110. Evidence that endogenous 6-(ARG or LYS)-opioid peptides can interact with kappa-receptors as agonists.
- Author
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Oka T and Negishi K
- Subjects
- Animals, Dynorphins, Endorphins pharmacology, Enkephalin, Methionine analogs & derivatives, Enkephalin, Methionine pharmacology, Enkephalins pharmacology, Male, Muscle Contraction drug effects, Protein Precursors pharmacology, Rabbits, Vas Deferens drug effects, Endorphins metabolism, Receptors, Opioid metabolism, beta-Endorphin analogs & derivatives
- Abstract
Evidence is provided for the abilities of endogenous 6-(Arg or Lys)-opioid peptides to interact with kappa-receptors as agonists. Dynorphin-(1-17) and -(1-8), alpha- and beta-neo-endorphin, [Met5]-enkephalin-Arg6-Phe7 and des acetyl salmon endorphin I significantly inhibited the electrically-evoked contractions of rabbit vas deferens which had been shown to contain kappa-receptors exclusively, indicating that endogenous 6-(Arg or Lys)-opioid peptides could act on kappa-receptors as agonists. Additionally, the inhibition of contractions of rabbit vas deferens by 6-(Arg or Lys)-opioid peptides was antagonized more effectively by Mr 2266 which had a high affinity to both mu- and kappa-receptors, than naloxone which had a high affinity only to mu-receptors. This also suggested that 6-(Arg or Lys)-opioid peptides acted as kappa-receptor agonists. The rank order of the inhibitory potency of 6-(Arg or Lys)-opioid peptides against contractions of rabbit vas deferens was as follows: dynorphin-(1-17) greater than alpha-neo-endorphin greater than beta-neo-endorphin .=. dynorphin-(1-8) greater than des acetyl salmon endorphin I greater than [Met5]-enkephalin-Arg6-Phe7. Since other endogenous opioid peptides such as [Met5]- and [Leu5]-enkephalin and beta-endorphin have been shown not to act on kappa-receptors as agonist, data in the present study suggest that endogenous opioid peptides can be classified into two groups in terms of an ability to interact with kappa-receptors as an agonist.
- Published
- 1982
- Full Text
- View/download PDF
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