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 intracerebroventricular administration of Substance P (SP) produced a marked and short-lasting increase in the threshold for vocalization and vocalization afterdischarge in the rat after electrical stimulation of the tail. This effect was blocked by naloxone and potentiated by bacitracin, a peptidase inhibitor. The analgesic effect of SP was also blocked by the concomitant intraventricular injection of the specific antibody against the opioid peptide metenkephalin but not by the antibody against beta-endorphin. Anti-met-enkephalin did not block other pharmacological actions of SP. The results suggest that SP produces an analgesic effect in rats by releasing met-enkephalin at supra-spinal levels involved in pain control.
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PMID:Analgesic activity of substance P in rats: apparent mediation by met-enkephalin release. 617 42

Intracerebroventricular (ICV) administration of the peptidase inhibitors amastatin, trasylol, bacitracin, or phe-D-ala and systemic administration of phenylmethylsulfonyl fluoride resulted in one or more of the following responses: analgesia, reduced withdrawal severity in opiate tolerant rats, alterations in motor activity and behavior, hypo- and hyperthermia and others; some of these effects were antagonized by naloxone, suggesting participation of opioid and other endogenous peptides. In addition, peptidase inhibitors enhanced analgesic and other responses to opioid peptides given ICV. Peptidase inhibition affords another method of inducing selective pharmacological responses such as pain relief in individuals resistant to other forms of therapy. ICV administration of beta-endorphin in the rat induces general anesthesia that is instantly reversed by systemic naloxone. Extensions of this work include identification of specific neural pathways that mediate anesthesia and characterization of opiate receptor subtype(s) at these sensitive loci. This approach offers the potential for the design of systemically effective opioid peptide anesthetics with little or no secondary effects and rapid reversibility.
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PMID:Newer concepts of analgesia and anesthesia. 619 95

This study concerned the fragmentation of beta-endorphin (beta-EP-(1-31) by synaptic membrane-bound peptidases. The peptides which accumulated during digestion of beta-endorphin by isolated synaptosomal plasma membrane preparations of rat brain were separated and isolated by high pressure liquid chromatography. Amino acid analysis of the peptide fractions indicated the formation of beta-EP-(1-21), beta-EP-(2-21) (pH 7.4), beta-EP-(18-31), beta-EP-(1-14), and beta-EP-(1-13) (pH 5.0) in addition to previously identified gamma-endorphin (beta-EP-(1-17)), alpha-endorphin (beta-EP-(1-16), and their des-tyrosine fragments (Burbach, J. P. H., Loeber, J. G., Verhoef, J., Wiegant, V. M., De Kloet, E. R., and De Wied, D. (1980) Nature 283, 96-97). The beta-endorphin fragments obtained with crude or with purified synaptosomal plasma membranes differed only quantitatively. The peptidase which converted gamma-endorphin into beta-EP-(1-16), beta-EP-(1-15), beta-EP-(1-14), and beta-EP-(1-13), was considerably active at pH 5.0 and resembled carboxypeptidase A in degrading gamma-endorphin; the activity was reduced by the carboxypeptidase A inhibitor D-phenylalanine. The data supplement previous findings and allow routes to be delineated for the conversion of beta-endorphin by brain synaptic membranes. A pathway comprising the main events in the conversion processes is proposed and is discussed in relationship to the significance of beta-endorphin as a precursor for neuropeptides with distinct central activities.
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PMID:Proteolytic conversion of beta-endorphin by brain synaptic membranes. Characterization of generated beta-endorphin fragments and proposed metabolic pathway. 627 86

Phosphorylated forms of corticotropin[ACTH (1-39)], corticotropin-like intermediary lobe peptide[CLIP, ACTH (18-39)], and the common precursor for ACTH and beta-lipotropin (beta-LPH) have been identified in extracts of rat pituitaries, 32P-Labeled inorganic phosphate was successfully incorporated into ACTH (1-39), CLIP, and the ACTH/beta-LPH precursor in rat neurointermediary lobe explants and into ACTH (1-39) in isolated rat anterior pituitary cells. After peptidase digestion of the labeled CLIP and ACTH, the radioactive phosphate was recoverable as O-phosphoserine. The serine residue at position 31 was the only amino acid found to be phosphorylated in CLIP and ACTH (1-39). The unphosphorylated forms of both peptides were also synthesized. The demonstration of he incorporation of [32P]phosphate into CLIP, ACTH (1-39), and the ACTH/beta-LPH precursor is consistent with the hypothesis that, within the rat intermediary lobe, phosphorylated CLIP is derived from a phosphorylated form of the common precursor, with phosphorylated ACTH (1-39) acting as a biosynthetic intermediate.
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PMID:Biosynthesis of phosphorylated forms of corticotropin-related peptides. 627 71

Various agents that have been reported to reduce the enzymatic degradation of the enkephalins have been tested for their ability to potentiate the activity of [Met5]enkephalin in three in vitro assay tissues. The greatest effect was obtained with the combination of bestatin (10 microM or 30 microM), captopril (10 microM), thiorphan (0.3 microM) and L-Leucyl-L-leucine (2 mM) which increased the potency of [Met5]enkephalin 18-fold in the guinea-pig myenteric plexus, 13-fold in the mouse vas deferens and 200-fold in the rat vas deferens. The increased potency is attributed to inhibition of the peptidases since the mixture of inhibitors did not change the activity of either normorphine or the metabolically stable synthetic opioid peptides. The potencies of the hexa-, hepta- and octapeptide C-terminus extensions of [Met5]enkephalin and [Leu5]enkephalin were increased by the peptidase inhibitors in all three preparations; the greatest effects were found in the rat vas deferens. No significant changes in the potencies of fragments of beta-endorphin longer than beta-endorphin-(1-19) were obtained. It may now be possible to inhibit enzymatic degradation of opioid peptides sufficiently to measure their release from neurones activated by electrical field stimulation.
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PMID:Increase in potencies of opioid peptides after peptidase inhibition. 629 58

In this manuscript, we provide evidence for the uptake of met-enkephalin by brain neurons. Tritiated met-enkephalin was accumulated by a crude synaptosomal fraction of rat brain, in the presence of peptidase inhibitors. Characterization of this process in striatum and mediobasal hypothalamus showed incubation time- and temperature-dependence and inhibition in part by several metabolic inhibitors. 3H-met-enkephalin uptake could be abolished in a dose-dependent manner by increasing concentrations of unlabelled met-enkephalin. Preincubation with naloxone resulted in up to 50% reduction of 3H-met-enkephalin uptake, suggesting a partial dependence on an opiate receptor interaction. 3H-met-enkephalin uptake was significantly reduced by freezing and thawing of the tissue preparation and completely abolished by addition of detergent or colchicine. The process showed dependence on substrate concentration, but was not saturable. Kinetic analysis of the 3H-met-enkephalin uptake revealed that the overall process best fit a transport model postulating the presence of a high-affinity, saturable uptake mechanism together with a second nonsaturable one. The uptake showed regional variation in brain with a distribution that closely paralleled those reported for met-enkephalin-like immunoreactivity and opiate receptor density. The precise significance of this 3H-met-enkephalin accumulation in brain remains to be determined. Whether this process represents 'reuptake' in the classical sense for termination of action, or internalization by some other process remains to be shown.
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PMID:Uptake/internalization of Met-enkephalin by brain synaptosomes. 666 15

The neurointermediary lobes from 190 rat pituitaries were homogenized in an acidic medium which inhibits peptidase activity and maximizes the solubilization of undamaged peptides. Octadecylsilyl-silica (ODS-silica) was used to extract the supernatant of the tissue homogenate. The ODS-silica eluate, now largely protein and salt free, was subjected to reversed-phase high-performance liquid chromatography (HPLC) employing 0.1% trifluoroacetic as counter ion. The column eluates were monitored for beta-endorphin immunoreactivity. Five immunoreactive components were observed. The most hydrophobic of these was repurified on the same HPLC column using 0.13% heptafluorobutyric acid as counter ion. Characterization of the purified peptide by gel permeation HPLC, amino acid analysis, and tryptic fragmentation indicated that it corresponded in structure to alpha-N-acetyl-beta-endorphin1-26. Amino acid analysis of the native peptide and its trypsin and carboxypeptidase fragments indicated that an alanyl residue occupies position 26. This finding is in contrast to the sequence predicted for the beta-lipotropin/corticotropin precursor by recombinant DNA techniques which suggests that the 26th residue of the beta-endorphin molecule should be valine.
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PMID:alpha-N-acetyl-beta-endorphin1-26 from the neurointermediary lobe of the rat pituitary: isolation, purification, and characterization by high-performance liquid chromatography. 684 89

alpha-MSH immunoreactive peptides were fractionated and characterized in rat and human brain and rat pituitary by reversed phase high pressure liquid chromatographic techniques. alpha-MSH and deacetylated alpha-MSH were two major naturally existing peptides in both brain and pituitary gland. Subsequent experiments examined the roles of these two peptides in neuronal function. The alpha-MSH was clearly more effective than deacetylated alpha-MSH in improving performance on a visual discrimination task after intraperitoneal administration and in inducing excessive grooming after intraventricular administration. The difference in behavioral potency may be explained by the fact that alpha-MSH was much more resistant to peptidase degradation than was deacetylated alpha-MSH. N-acetylation of alpha-MSH may be an effective regulatory process for modulating the behavioral potency of the secretory product of alpha-MSH-containing pituitary cells and neurons.
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PMID:Evidence that N-acetylation regulates the behavioral activity of alpha-MSH in the rat and human central nervous system. 730 40

Neuroleptic drugs have been shown to affect the level and messenger ribonucleic acid of specific neuropeptides. The effect of subchronically administered neuroleptics on neuropeptide metabolism, however, has not been systematically characterized. In the present study, the effect of neuroleptics and other dopaminergic compounds on substance P (SP), cholecystokinin and met-enkephalin degradation was determined on intact, regional, rat brain slices. After 7-day administration of haloperidol (1 mg/kg) or chlorpromazine (20 mg/kg), SP degradation was decreased in caudate-putamen and nucleus accumbens. After administration of the dopaminergic agonist apomorphine (5 mg/kg, b.i.d.), SP degradation was increased in the nucleus accumbens. The dopamine D2-receptor antagonist sulpiride (100 mg/kg, b.i.d.) produced no effect on SP degradation. Met-enkephalin degradation was decreased after haloperidol administration in both frontal cortex and caudate-putamen and unaffected by apomorphine administration. The metabolism of cholecystokinin was not affected by neuroleptic treatment. Studies performed with specific peptidase inhibitors suggested that neutral endopeptidase 24.11, metalloendopeptidase 24.15 and aminopeptidases degrade SP on caudate-putamen and nucleus accumbens slices. Therefore, alterations in these peptidases may be responsible for the change noted in SP degradation after dopaminergic compound administration. These metabolic changes noted after neuroleptic administration may therefore contribute to neuroleptic-induced alterations in regional peptide levels.
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PMID:Neuropeptide metabolism on intact, regional brain slices: effect of dopaminergic agents on substance P, cholecystokinin and Met-enkephalin degradation. 754 72

1. Cholinergic contraction was induced in segments of rat jejunum by transmural stimulation (10 Hz, 1 ms for 8 s). The synthetic delta-opiate agonist, DADLE (100 nM), caused a prolonged inhibition of the cholinergic response. 2. The naturally occurring opioid peptides, dynorphin A (1-13) (200 nM), leu-enkephalin (400 nM), met-enkephalin (200 nM) and the synthetic delta-agonist, DSLET (30 nM), also caused large inhibitions in the response. 3. Each of these peptides lost a significant amount of their original activity at 6 min, which was reduced by a mixture of peptidase inhibitors consisting of bestatin (30 microM), thiorphan (10 microM), captopril (10 microM) and L-leucyl-L-leucine (2 mM). 4. The enkephalinase inhibitor, thiorphan (10 microM), significantly lengthened the time at which met-enkephalin was active, but not to the same extent as the mixture of peptidase inhibitors. However, the mixture of peptidase inhibitors did not significantly alter the cholinergic contraction in the absence of opioid peptides. 5. It is concluded that peptidases, including enkephalinase, are present in the rat intestine. However, the model presently described does not release functional amounts of endogenous opioid peptides, nor does it become tolerant to the effect of stimulating its delta-opioid receptors.
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PMID:Evidence for peptidase activity in the rat intestine. 767 74


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