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)

Plasma beta-endorphin, met-enkephalin and ACTH concentrations were measured in 20 male alcoholics (age: 32-60 yr; duration of ethanol addiction: 13.2 +/- 6.2 yr; mean +/- SE) immediately after admission to the hospital (at a time not exceeding 8 hr from the last ethanol consumption) and after 5 weeks of forced abstinence. The results were compared with those obtained in 12 age-matched normal controls. Plasma ACTH and met-enkephalin levels were normal in alcoholics on both occasions. In contrast, in samples taken at admission to the hospital, the circulating concentrations of beta-endorphin in alcoholics were half (17.1 +/- 5.3 pg/ml; mean +/- SE) of those observed in the normal controls (34.1 +/- 6.0). beta-endorphin levels rose significantly after 5 weeks of abstinence (30.1 +/- 4.9); at this time, they were not significantly different from those observed in normal controls. These data indicate that acute alcohol consumption induces significant alterations in plasma beta-endorphin, but not met-enkephalin levels, which are reversed after 5 weeks of abstinence.
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PMID:Plasma beta-endorphin, but not met-enkephalin levels are abnormal in chronic alcoholics. 133 22

At this time, 27 years after the initial studies on development of methadone for the maintenance treatment of opiate addiction were begun, it has been shown that [table; see text] methadone meets most criteria for a pharmacologic agent for chronic treatment of an addiction. It is effective after oral dosing: it has a long biological half-life in humans, it causes minimal side effects when used in chronic treatment, and it has no true toxic effects or serious side effects. Also methadone has been shown to be very effective when appropriately used in programs which combine pharmacotherapy with the best elements of "drug free" treatment, that is, counseling and psychological support. In addition to pharmacological treatment, there should be access to, if not on-site, medical and behavioral care as needed, as well as linkage to resources for various aspects of rehabilitation. At this time many of the actions, as well as the specific sites of action, and mechanisms of actions of methadone as used in chronic treatment of opiate addiction have been defined by scientific experimentation, both at the preclinical and clinical levels. It is known that methadone prevents abstinence symptoms, prevents drug hunger or craving, blocks euphorogenic effects of other opiates, and prevents relapse to illicit use of opiates. It is known that the site of action of methadone is at specific opioid receptors. Research to date suggests that there is no demonstrable down-regulation or up-regulation of opioid receptors during chronic opioid agonist perfusion, although chronic administration of the opioid antagonist naltrexone does appear to up-regulate opioid receptors. Clinical studies show that chronic use of methadone allows normalization of release and peripheral levels of one of the classes of endogenous opioids, beta-endorphin, and the related peptides derived from POMC released and processed from the anterior pituitary in humans. Also levels of beta-endorphin in cerebrospinal fluid become normal during chronic maintenance treatment, reflecting apparently normal processing and release of beta-endorphin at brain or hypothalamic sites of POMC production. Available data from studies of beta-endorphin indicate that there is a [table; see text] normalization, rather than disruption, of the endogenous opioid system in general during steady state administration of methadone, as contrasted with intermittent dosing and then abrupt withdrawal of short-acting opiates such as heroin. Although there is still much to be learned about the neurobiology of opiate addiction, at this time we do know a great deal about the effects of opiates and opioids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Rationale for maintenance pharmacotherapy of opiate dependence. 134 39

The detailed information now available regarding the neurobiology of opiates (opioids) has contributed greatly to our understanding of opioid addiction. This in turn has permitted a more complete understanding of the processes underlying drug addiction. Opioid agonists with a high affinity for mu- or delta-receptors produce conditioned preferences for an environment previously associated with their administration, whereas kappa-agonists induce place aversions. Studies in which opioids were microinjected into discrete brain areas suggest that these opposing motivational effects are mediated via an interaction with the mesolimbic dopamine (DA) system originating in the midbrain. Microdialysis studies have clearly shown that mu-agonists preferentially increase DA release and metabolism in the Nucleus accumbens, whereas kappa-receptor agonists decrease release. Opposite effects on DA are observed in response to microinjections of selective antagonists for these receptor types, suggesting the existence of tonically active endogenous opioid systems which maintain DA release in the mesolimbic system: a continuous "reward" tone, probably mediated by beta-endorphin in the ventral tegmentum of the midbrain and an "aversive" tone, mediated by dynorphin in the Nucleus accumbens. Aspects of such a bidirectional regulation of the mesolimbic system by endogenous opioids are discussed.
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PMID:[Opiate addiction. Pharmacologic and biochemical aspects]. 158 96

Peptides derived from pro-opiomelanocortin (POMC) influence neurodevelopmental processes. Earlier studies indicated that MSH/ACTH compounds improved behavioral efficiency in retarded individuals. Recent studies have shown that opiate blockers reduce treatment-resistant self-injurious behavior (SIB), an autistic-like, developmental disorder. Although the exact mechanisms are unknown, prenatal POMC disregulation, addiction to endogenous opiates and elevated pain threshold have been proposed to account for this behavior. In study one, four SIB patients were given 0, 25, 50 or 100 mg of naltrexone on separate weeks in a double blind, Latin square design. A specific dose dependent reduction in SIB was observed in three patients. In study two, plasma b-endorphin was measured in 40 patients with SIB, a related behavior, stereotypy (ST) or controls. SIB and ST patients had higher levels of endorphin than controls. These data added new support for the role of b-endorphin in a treatment-resistant patient group.
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PMID:Beta-endorphin disregulation in autistic and self-injurious behavior: a neurodevelopmental hypothesis. 246 89

The effects of drug abuse are caused by the stimulation or inhibition of different neurotransmitters, chiefly gamma-aminobutyric acid, acetylcholine, norepinephrine, dopamine, serotonin and beta-endorphin. The biopsychiatric model focuses on neurotransmitter activity to diagnose and treat overdose and addiction. This model explains how different drugs exert their effects and provides a rationale for specific pharmacologic intervention in the drug-abusing patient.
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PMID:Drug abuse: a biopsychiatric model. 239 62

Endogenous opioid systems may be altered as a consequence of addiction, but evidence to support this idea is meager so far. We obtained 136 cerebrospinal fluid (CSF) samples from 72 opioid addicts during four distinct states: methadone maintenance, detoxification from methadone, opioid antagonist treatment, and drug-free status. CSF endorphins were measured in 86 patients samples using a radioreceptor assay (RRA), and beta-endorphin levels were measured in 85 patient samples using a radioimmuno assay (RIA). During detoxification, both RRA fraction I and beta-endorphin showed a generally similar pattern of changes. Both were lowest when measured 40-50 hr after the last opioid dose, and both showed an apparent rebound to higher than methadone maintenance values at 60-70 hr following the last dose. During methadone maintenance and drug-free states, the addicts' levels of fraction I RRA endorphins in the CSF were higher than levels found in a normal control group. Fraction II endorphins were also elevated in the addicts who were drug free. In contrast, CSF beta-endorphin during both methadone maintenance and drug-free states was lower in the addicts as compared to the normal, drug-naive group. Except for the pattern found during detoxification, there were no consistent changes in endorphin levels across different states of addiction.
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PMID:Endogenous opioids in cerebrospinal fluid of opioid-dependent humans. 284 15

Bulimia, a disorder of episodic binging and purging, remains without a known etiology. A case report is presented of a patient who attributed bulimic episodes to efforts at inducing euphoria. Experimental pain tolerance was increased by bulimic vomiting, blocked by naloxone, but not by saline. Vomiting was also associated with falls in depression and anxiety. Plasma ACTH and cortisol, putative markers for beta-endorphin, also rose following vomiting. It is hypothesized that in some bulimics, the disorder arises by virtue of an addiction to one's own internally released endogenous opioid peptides.
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PMID:Bulimic vomiting alters pain tolerance and mood. 303 Sep 47

Opiate addiction and stress have been associated with altered immune responses. In this study, we evaluated the influence of morphine and the stress responsive opioid peptide beta-endorphin (beta-END) on O-2 and H2O2 production by cultured human peripheral blood mononuclear cells. Exposure of these cells during 48 hr of culture to morphine and beta-END at pharmacologically (10(-8) M) and physiologically (10(-12) M) relevant concentrations, respectively, markedly suppressed peripheral blood mononuclear cell O-2 and H2O2 release in response to the respiratory burst stimuli opsonized zymosan and phorbol myristate acetate. Both opioids also induced a minimal, but statistically significant, increase in resting O-2 and H2O2 generation. The modulatory effects of morphine and beta-END on peripheral blood mononuclear cell oxygen metabolism appeared to involve a classical opioid receptor, because opioid activity was blocked by naloxone and was not observed with N-acetylated-beta-END. Using purified lymphocyte and monocyte preparations, we determined that although opioids directly increase monocyte-resting oxygen metabolism, lymphocytes are the primary target cell in opioid-mediated suppression of monocyte respiratory burst activity. The release of a suppressive product from opioid-triggered lymphocytes was inhibited by cyclosporine. Based on the results of this study, we propose that opioid-mediated suppression of mononuclear phagocyte respiratory burst activity is another factor to be considered in the immunodeficiency of opiate addiction and stress.
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PMID:Opioid-mediated suppression of cultured peripheral blood mononuclear cell respiratory burst activity. 303 15

Mounting evidence suggests that opiate addiction and stress are associated with impaired cell-mediated immunity. We tested the hypothesis that morphine and the endogenous opioid beta-endorphin (beta-END), a pituitary peptide released in increased concentrations during stress, can suppress the production of the key macrophage-activating lymphokine interferon-gamma (IFN-gamma) by cultured human peripheral blood mononuclear cells (PBMNC). Using a radioimmunoassay to measure IFN-gamma, we found that exposure of PBMNC to biologically relevant concentrations of both opioids significantly inhibited IFN-gamma generation by cells stimulated with concanavalin A and varicella zoster virus. Studies of the mechanism of suppression revealed (a) a classical opioid receptor is involved (suppression was antagonized by naloxone and was specific for the NH2 terminus of beta-END), (b) monocytes are the primary target cell for opioids (monocyte-depleted lymphocyte preparations showed little suppression), and (c) reactive oxygen intermediates (ROI) and prostaglandin E2 are important mediators (scavengers of ROI and indomethacin eliminated the suppression). Based on these findings we suggest that opioid-triggered release of inhibitory monocyte metabolites may play a role in the immunodeficiency associated with narcotic addiction and stress.
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PMID:Opioid-mediated suppression of interferon-gamma production by cultured peripheral blood mononuclear cells. 304 Aug 7

Our presently somewhat limited knowledge of the modulation of the content, release and turnover of endorphins in brain and pituitary by acute and chronic drug treatment is reviewed and discussed particularly in relation to the problem of addiction. In vitro studies in striatal slices and isolated anterior and intermediate/posterior lobes of the pituitary point to the existence of specific interactions between endorphins and neurotransmitters. In vivo studies have revealed acute GABA-mediated effects of benzodiazepines upon striatal levels of met-enkephalin activity. Morphine exerts no acute effects upon endorphin levels, but decreases the levels of particular endorphins in specific areas of brain and pituitary after long-term treatment; somewhat similar effects are observed after prolonged intake of ethanol, whereas chronic haloperidol treatment results in an increase in levels of endorphins in brain and pituitary. Incorporation studies employing the intermediate/posterior lobe of the pituitary have revealed that the changes in beta-endorphin levels produced by prolonged treatment with morphine or haloperidol reflect a respective depressed or enhanced synthesis of the beta-endorphin precursor pro-opiocortin, whilst the enzymatic processing of this precursor remains unmodified. Studies in cell-free preparations demonstrated that m-RNA extracted from the intermediate/posterior lobes of chronically morphinized rats possesses a decreased "activity".
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PMID:Pharmacological modulation of opiate-like peptide systems. 611 2


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