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)

Exercise and the endogenous opioids have been linked to anorexia nervosa. This investigation determined the effects of the weight-loss syndrome induced by voluntary exercise (22.5 h/day) in food-restricted rats (1.5 h/day food access) on the endogenous opioids. The animals were tested under resting-fed and 2-deoxy-D-glucose (2DG) stimulated conditions. Weight-matched, freely fed exercised and ad libitum fed unexercised groups served as controls. Specific opioid abnormalities were found in the syndrome. These included a basal elevation in plasma beta-endorphin, which was abnormally suppressed by 2DG, and 2DG-induced elevations in arcuate hypothalamic beta-endorphin content and supraoptic hypothalamic dynorphin-A content. None of these changes occurred in controls. Finally, it was found that short-term moderate exercise itself chronically reduced adenohypophysial beta-endorphin content and elevated supraoptic dynorphin-A content. The relationship of the syndrome's hyperendorphinism to the hypothalamo-pituitary-adrenal axis and the auto-addiction hypothesis of anorexia nervosa was considered, as was the significance of the supraoptic dynorphin-A abnormality to the hypothalamo-neurohypophysial system. The differential sensitivity of the supraoptic dynorphin-A system compared to the arcuate hypothalamic beta-endorphin system to moderate exercise was also discussed.
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PMID:Beta-endorphin and dynorphin abnormalities in rats subjected to exercise and restricted feeding: relationship to anorexia nervosa? 790 87

The biochemical and cellular mechanisms involved in the development and/or maintenance of morphine tolerance remain unclear. In the adult central nervous system (CNS) results are contradictory. For the neonate, a variety of drug induced deficits have been observed following prenatal addiction to opioids, although very little work on the biochemical and molecular level has been done. Therefore, the present study was carried out to investigate the effects of prenatal morphine treatment on the levels and expression of endogenous opioid peptides in brain regions of newborns. Dams were implanted with one morphine pellet (75 mg each) 1 week prior to the birth of pups. Changes in mRNA levels for the opioid peptides were determined by Northern blot analysis. Alterations in opioid peptide levels were determined by radioimmunoassays. Prenatal morphine treatment significantly increased proenkephalin mRNA levels and decreased met-enkephalin levels in striatum of newborns. These data are in contrast to what is observed in the adult CNS. These data indicate that prenatal morphine treatment may increase met-enkephalin release and/or cause inhibition at the level of translation. In addition, increased transcription may be necessary to maintain equilibrium in the system when there is an increase in met-enkephalin release.
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PMID:Prenatal morphine exposure differentially alters expression of opioid peptides in striatum of newborns. 875 Aug 81

Adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone (alpha-MSH) are centrally acting melanocortin peptides with numerous reported functions, including induction of excessive grooming and antipyresis, among others. Also reported is a role for melanocortins in aspects of opiate action. Although early work examined the effects of ACTH and MSH on opiate-induced behaviors, further progress has been limited. Recently, however, advances in the identification and characterization of melanocortin receptor (MC-R) subtypes have provided novel tools with which to study interactions between melanocortins and addiction. The present review discusses the effects of ACTH and MSH on opiate-induced behaviors and relates these findings to more recent reports on the regulation of melanocortin systems by exogenous opiates. Emerging from these data is the possibility that melanocortin receptor activation, specifically at the MC4-R subtype, may act to antagonize certain properties of exogenous opiates, including perhaps addiction.
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PMID:Melanocortins and opiate addiction. 920 Jun 63

Cocoa and chocolate contain the tetrahydroisoquinoline alkaloid salsolinol up to a concentration of 25 microg/g. Salsolinol is a dopaminergic active compound which binds to the D(2) receptor family, especially to the D(3) receptor with a K(i) of 0.48+/-0.021 micromol/l. It inhibits the formation of cyclic AMP and the release of beta-endorphin and ACTH in a pituitary cell system. Taking the detected concentration and the pharmacological properties into account, salsolinol seems to be one of the main psychoactive compounds present in cocoa and chocolate and might be included in chocolate addiction.
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PMID:In vitro pharmacological activity of the tetrahydroisoquinoline salsolinol present in products from Theobroma cacao L. like cocoa and chocolate. 1102 51

The human mu opioid receptor (MOR) plays a central role in mediating the effects of opioids, both endogenous and exogenous. Epidemiological studies have shown that addiction in general, and especially opiate addiction, has a heritable component. Clinical and laboratory studies suggest that the MOR gene may contribute to the heritable component of vulnerability to develop opiate addiction. Naturally occurring single nucleotide polymorphisms (SNPs) have been identified in the MOR gene by conventional methods. Two coding region SNPs, the A118G and C17T substitutions, occur at high allelic frequencies (10.5% and 6.6%, respectively, in our previous studies). These common SNPs cause amino acid changes in the receptor, and may have implications for differences in individual responses to opioids, as well as decreased or increased vulnerability to opiate addiction. The A118G substitution encodes a variant receptor with binding and signal transduction differences in response to beta-endorphin in cellular assays. Recent innovations in microchip technology offer new potential methods for SNP detection. We report here on the development of two separate approaches using custom oligonucleotide gelpad microarrays for detection of these two common SNPs of the MOR gene in human DNA samples. First, PCR-amplified genomic DNA samples were used to produce target sequences, which were labeled with fluorescent dye and hybridized to custom microchips. Oligonucleotides on these reusable microchips were designed to query nucleotide substitutions at positions 17 and 118 of the MOR gene. Thirty-six human DNA samples were assayed both on these custom microchips and by conventional automated gel sequencing, with highly concordant identification of both heterozygous and homozygous substitutions. A second approach was developed for the C17T SNP utilizing single nucleotide extension on custom microchips. These custom gelpad microchips have potential for the rapid and inexpensive detection of specific SNPs for genetic and genomic studies.
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PMID:Detection of single nucleotide polymorphisms of the human mu opioid receptor gene by hybridization or single nucleotide extension on custom oligonucleotide gelpad microchips: potential in studies of addiction. 1105 67

The endogenous opioid system consists of three opioid peptide precursor genes encoding enkephalins (preproenkephalin, Penk), dynorphins (preprodynorphin, Pdyn) and beta-endorphin (betaend), proopiomelanocortin (POMC) and three receptor genes encoding mu-opiod receptor (MOR), delta-opiod receptor (DOR) and kappa-opiod receptor (KOR). In the past years, all six genes have been inactivated in mice by homologous recombination. The analysis of spontaneous behavior in mutant mice has demonstrated significant and distinct roles of each gene in modulating locomotion, pain perception and emotional behaviors. The observation of opposing phenotypes of MOR- and DOR-deficient mice in several behaviors highlights unexpected roles for DOR to be further explored genetically and using more specific delta compounds. The analysis of responses of mutant mice to exogenous opiates has definitely clarified the essential role of MOR in both morphine analgesia and addiction, and demonstrated that DOR and KOR remain promising targets for pain treatment. These studies also show that prototypic DOR agonists partially require MOR for their biological activity and provide some support for the postulated mu-delta interactions in vivo. Finally, data confirm and define a role for several genes of the opioid system in responses to other drugs of abuse, and the triple opioid receptor knockout mutant allows exploring non-classical opioid pharmacology. In summary, the study of null mutant mice has extended our previous knowledge of the opioid system by identifying the molecular players in opioid pharmacology and physiology. Future studies should involve parallel behavioral analysis of mice lacking receptors and peptides and will benefit from more sophisticated gene targeting approaches, including site-directed and anatomically-restricted mutations.
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PMID:Exploring the opioid system by gene knockout. 1201 97

Lewis rats that are known to be addiction-prone, develop compulsive running if they have access to running wheels. The present experiments were aimed 1) to evaluate the activation of stress systems following chronic and acute voluntary wheel running in Lewis rats by measurement of hormone release and gene expression of neuropeptides related to hypothalamic-pituitary-adrenocortical (HPA) axis activity and 2) to test the hypothesis that wheel running as a combined model of addictive behavior and stress exposure is associated with modulation of ionotropic glutamate receptor subunits in the ventral tegmental area. Voluntary running for three weeks but not for one night resulted in a rise in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels (p<0.05) compared to those in control rats. Principal component analysis revealed the relation between POMC gene expression in the intermediate pituitary and running rate. Acute exposure of animals to voluntary wheel running induced a significant decrease in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit mRNA levels (p<0.01), while repeated voluntary physical activity increased levels of GluR1 mRNA in the ventral tegmentum (p<0.05). Neither acute nor chronic wheel running influenced N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA levels in the ventral tegmental area. Thus, the present study revealed changes in AMPA receptor subunit gene expression in a reward-related brain structure as well as an activation of HPA axis in response to compulsive wheel running in Lewis rats. It may be suggested that hormones of HPA axis and glutamate receptors belong to the factors that substantiate higher vulnerability to addictive behavior.
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PMID:Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats. 1272 36

The most prevalent single-nucleotide polymorphism (SNP) A118G in the human mu-opioid receptor gene predicts an amino acid change from an asparagine residue to an aspartatic residue in amino acid position 40. This N40D mutation, which has been implicated in the development of opioid addiction, was previously reported to result in an increased beta-endorphin binding affinity and a decreased potency of morphine-6-glucuronide. Therefore, in the present study we have investigated whether this mutation might affect the binding affinity, potency, and/or the agonist-induced desensitization, internalization and resensitization of the human mu-opioid receptor stably expressed in human embryonic kidney 293 cells. With the exception of a reduced expression level of N40D compared to human mu-opioid receptor (hMOR) in HEK293 cells, our analyses revealed no marked functional differences between N40D and wild-type receptor. Morphine, morphine-6-glucuronide and beta-endorphin revealed similar binding affinities and potencies for both receptors. Both the N40D-variant receptor and hMOR exhibited robust receptor internalization in the presence of the opioid peptide [d-Ala(2),N-MePhe(4),Glyol(5)]enkephalin (DAMGO) and beta-endorphin but not in response to morphine or morphine-6-glucuronide. After prolonged treatment with morphine, morphine-6-glucuronide or beta-endorphin both receptors showed similiar desensitization time courses. In addition, the receptor resensitization rates were nearly identical for both receptor types.
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PMID:Effect of the A118G polymorphism on binding affinity, potency and agonist-mediated endocytosis, desensitization, and resensitization of the human mu-opioid receptor. 1508 12

The role of alcohol consumption and alcoholism as an addiction in regulating the chemistry of the brain and its physiology has gained a backlog of interest over the past few decades. Besides the notion that alcohol acts as a brain depressant, the molecular mechanisms and neuronal interactions are not well understood. Emerging evidence implicates alcohol as a neurochemical messenger that influences a cross talk amongst the nervous, immune, and endocrine systems. Specifically, alcohol acts as a crucial regulator of the hypothalamic-pituitary-adrenal (HPA) axis, thereby modulating the release of hormones, particularly adrenocorticotropic hormone (ACTH) and corticosterone (CORT). It is the aim of this review, therefore, to investigate current concepts on how alcohol, particularly ethanol, and alcoholism affect neuro-immune-endocrine neurochemical interactions via the regulation of the HPA axis, taking into consideration bio-behavioral and physiochemical aspects.
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PMID:Alcoholism and neuro-immune-endocrine interactions: physiochemical aspects. 1536 60

Overproduction of corticotropin-releasing hormone (CRH) and stress system abnormalities are seen in psychiatric diseases such as depression, anxiety, eating disorders, and addiction. Investigations of CRH type 1 receptor (CRHR1) nonpeptide antagonists suggest therapeutic potential for treatment of these and other neuropsychiatric diseases. However, overproduction of CRH in the brain and on its periphery and disruption of the hypothalamic-pituitary-adrenal axis are also found in 'somatic' disorders. Some rare forms of Cushing's disease and related pituitary/adrenal disorders are obvious applications for CRHR1 antagonists. In addition, however, these antagonists may also be effective in treating more common somatic diseases. Patients with obesity and metabolic syndrome who often have subtle, but chronic hypothalamic-pituitary-adrenal hyperactivity, which may reflect central dysregulation of CRH and consequently glucocorticoid hypersecretion, could possibly be treated by administration of CRHR1 antagonists. Hormonal, autonomic, and immune aberrations are also present in chronic inflammatory, autoimmune, and allergic diseases, with considerable evidence linking CRH with the observed abnormalities. Furthermore, autonomic dysregulation is a prominent feature of common gastrointestinal disorders, such as irritable bowel syndrome and peptic ulcer disease. Patients with irritable bowel syndrome and other gastrointestinal disorders frequently develop altered pain perception and affective symptoms. CRH acts peripherally to modulate bowel activity both directly through the autonomic system and centrally by processing viscerosensory and visceromotor neural signals. This review presents clinical and preclinical evidence for the role of CRH in the pathophysiology of these disorders and for potential diagnostic and therapeutic applications of CRHR1 antagonists. Recognition of a dysfunctional stress system in these and other diseases will alter the understanding and treatment of 'psychosomatic' disorders.
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PMID:Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in psychosomatic disorders. 1552 86


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