Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite the variability in sampling and methodology, the majority of the family, twin and adoption studies suggest that alcoholism is familial, a significant proportion of which can be attributed to genetic factors. However, the specific components of alcoholism that may be inherited have yet to be identified. To date, there are no biological trait markers for which there is evidence for specificity for alcoholism. The three major levels of enquiry regarding possible mechanisms for the transmission of alcoholism and the involvement of genes and gene products in its development are factors related to exposure, metabolism, or pharmacological effects of ethanol. Exposure to ethanol is an obvious precondition for the development of tolerance and/or dependence. Therefore, identification of factors which enhance (or decrease) exposure are important goals of studies of the pathogenesis of alcoholism. It is likely that demographic, cultural and environmental factors (i.e. sex, age, religious affiliation, social group influences, income, availability of alcohol, etc.) play a crucial role in mediating exposure to alcohol. The key to alcoholism is likely to reside in the effects of alcohol on the brain. In contrast to nicotine, the opioids, and catecholamines, no specific receptor for ethanol has been found. Thus, one major focus of current research on possible central nervous system (CNS) mechanisms for the effect of alcohol includes assessment of the role of alcohol in the stimulation of brain reward or reinforcement systems. Alternately, alcohol may produce dependence by normalizing abnormal baseline states such as irritability, hyperexcitability, dysphoria, impulsiveness, or stress/tension level. The results of animal studies have yielded information on the central effects of alcohol including sensitivity of neuronal membranes, proteins, and ion channels to alcohol, and factors related to the binding and release of neurotransmitters and neuromodulators including dopamine, norepinephrine, gamma aminobutyric acid, pro-opiomelanocortin, glutamate receptors and the endorphin system (Institute of Medicine, 1987). In addition to possible genetic explanations for the strong degree of familial aggregation of alcoholism, alternative explanations need to be further evaluated. These include: modelling of parental behaviour; possible changes in the susceptibility of the foetus to alcohol as a result of in utero maternal ingestion of alcohol; results of negligent rearing manifested in dietary deficiency, exposure to toxic substances, or brain trauma, which so often characterize the homes of alcoholic parents; or damage to paternal germ cells from alcohol.
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PMID:The genetic epidemiology of alcoholism. 218 16

D-Met2, Pro5-enkephalinamide (DMPEA) is an opioid peptide having analgesic activity in animals more potent after intravenous administration than morphine. It is less toxic but in animals it showed a higher dependence capacity than morphine. Besides analgesia DMPEA produces in rodent behavioral symptoms similar to those evoked by morphine or beta-endorphin, resembling the actions of neuroleptica. In human trials DMPEA was found to produce unpleasant sensations, no euphoria, and sometimes even dysphoria. DMPEA increases the serum levels of prolactin, growth hormone and, to a less extent, of TSH. Those effect of DMPEA on pituitary hormones. Finally, the human studies indicated that DMPEA antagonized pain (measured with the submaximum effort tourniquet technique), but did not affect adversely and even improved attention and short-term memory; it had no effect on the long-term memory. As the subjective effects of DMPEA are not pleasant, and no patient desired to obtain another treatment, some optimism as to low habit-forming properties of DMPEA may be justified.
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PMID:Pharmacological and human studies with a highly potent opioid peptide, D-Met2, Pro5-enkephalinamide. 333 15

The space adaptation syndrome is one of the more vexing problems confronted by our nation's astronauts during their journeys. This syndrome may be a variant of motion sickness, although this possibility has been questioned. Physostigmine, a centrally active cholinesterase inhibitor which increases brain acetylcholine, was found to cause a motion sickness-like syndrome--in psychiatric patients and normals--including nausea, emesis, malaise, dysphoria, increases in serum ACTH, beta-endorphin, cortisol, and prolactin, Neostigmine, a non-centrally acting cholinesterase inhibitor, and saline placebo caused no such effects. The above effects closely parallel those of motion sickness. Thus, the effects of physostigmine may be a convenient model for screening for treatments for motion sickness or space adaptation syndrome, or for predicting who will develop these syndromes.
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PMID:A cholinomimetic model of motion sickness and space adaptation syndrome. 648 3

Alcohol exerts numerous pharmacological effects through its interaction with various neurotransmitters and neuromodulators. Among the latter, the endogenous opioids play a key role in the rewarding (addictive) properties of ethanol. Three types of opioid receptors (mu, delta and kappa) represent the respective targets of the major opioid peptides (beta-endorphin, enkephalins and dynorphins, respectively). The rewarding (reinforcing) properties of mu- and delta-receptor ligands are brought by activation of the mesolimbic dopamine system which ascends from the ventral tegmentum of the midbrain (VTA) to rostral structures; of these, the nucleus accumbens (NAC) is of particular importance in drug addiction. In contrast, dysphoria results from activation of kappa-receptors. The neurochemical manifestations of these opposing effects are, respectively, increases and decreases in dopamine release in the NAC. Several lines of evidence indicate that alcohol interferes with endogenous opioid mechanisms which are closely linked with dopamine transmission in the mesolimbic pathway. The view that condensation products of dopamine and alcohol-derived aldehyde (tetrahydroisoquinolines) play a role remains controversial. There is, however, much information on the direct (acute and chronic) effects of alcohol on the binding properties of opioid receptors, as well as modulation of opioid peptide synthesis and secretion (e.g. a suggested increase in beta-endorphin release). In view of the reinforcing properties of alcohol, it is relevant to consider behavioural studies involving alcohol self-administration in rodents and primates. Low doses of morphine have been found to increase, and higher doses of the opiate to decrease, alcohol consumption. Conversely, opioid antagonists such as naloxone and naltrexone (which bind to non-selectively opioid receptors) have been shown to decrease alcohol consumption under various experimental conditions. Similar results have been reported when selective mu- or delta-receptor antagonists are administered. Results obtained in genetic models of high preference for alcohol also support the view that alcohol intake depends on the activity of the endogenous opioid reward system and that alcohol consumption may serve to compensate for inherent deficits in this system. One hypothetical model proposes that reward results from activation of mu-opioid receptors in the VTA and/or delta-receptor in the NAC; both these nuclei are targets of endogenous beta-endorphin. It is suggested that alcohol interferes with this reward pathway either directly or indirectly. The available experimental data accord well with those obtained from clinical studies which opioid antagonists have been used to prevent relapse in alcoholics. Conceptual considerations concerning communalities between various forms of addictions are also discussed in this review.
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PMID:Endogenous opioid systems and alcohol addiction. 904 Jan 15