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)

In studying the interactions between handling mice and their subsequent analgesic response to an intrathecally (i.t.) administered mu-opioid agonist, DAMGO, it was found that suspending ICR mice by the tail for 1, 5, or 20 sec, 10 min before the tail-flick test, enhanced DAMGO by 5.3-, 7.4- and 23.6-fold, respectively, compared with mice maintained in a level posture. This enhancement was not accompanied by a change in the rostral flow of [3H]-DAMGO (25 ng, i.t.) to the brain (3.7% in 10 min), in its distribution along the neuraxis or in its systemic absorption. However, i.c.v. administration of beta-endorphin (1-27), an antagonist of epsilon opioid receptors, abolished the enhancement of i.t. DAMGO without affecting its basal analgesic potency. Pretreatment with the delta-opioid antagonist naltrindole (5.6 nmol, i.t.,-30 min) also blocked the enhancement of DAMGO without significantly affecting its basal analgesic potency. Alternatively, this same dose of naltrindole injected i.c.v. failed to block the enhancement of DAMGO in suspended mice. A 20-sec suspension failed to enhance i.t. kappa and delta-agonists, but it did enhance i.t. morphine. In mouse strain comparisons, i.t. DAMGO was more potent in C57BL/6J and DBA/2J mice than in C3H/HeJ and ICR mice, but DAMGO was enhanced by a 20-sec suspension in all strains tested. Thus suspending mice by the tail evoked a reflex enhancement of spinal mu agonist-induced analgesia that probably involved both the supraspinal release of beta-endorphin (an endogenous epsilon agonist) and the subsequent spinal release of an endogenous delta-receptor agonist in the reflex pathway.
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PMID:Endogenous opioids released by suspending mice by the tail selectively enhance spinal mu opioid analgesia. 793 69

The effect of a beta-endorphin cleavage product devoid of opioid effects, des-tyrosine-gamma-endorphin (DT gamma E) on the neocortical spike-and-wave spindling episodes in the electrocorticogram (ECoG) of DBA/2J mice was studied. DT gamma E (0.01-1.0 mg/kg, i.p.) dose dependently reduced the spike-and-wave bursts duration. However, the low dose did not induce consistent modifications of the spike-and-wave bursts number while the dose of 0.1 and 1.0 mg/kg induced a progressive diminution. Furthermore, at all doses DT gamma E did not induce any alterations of the spike-and-wave bursts amplitude, frequency, and desynchronized activity when compared to the pre-drug period. These results indicate that this beta-endorphin fragment may affect brain excitability.
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PMID:Effect of des-tyrosine-gamma-endorphin on neocortical spike-and-wave spindling in DBA/2J mice. 800 46

Ethanol has been shown to enhance the in vitro release of hypothalamic beta-endorphin (beta-EP). In the present study, the pattern of beta-EP release by the hypothalamus of two strains of mice, bred selectively for their preference (C57BL/6) or aversion (DBA/2) to ethanol, was investigated using a tissue perifusion system. The tissues were perifused with 20 mM ethanol for 30 min and the immunoreactive beta-EP content was estimated in perifusates collected every 2 min. Ethanol induced an enhanced release of hypothalamic beta-EP characterized by an initial spike followed by a gradual decrease toward baseline levels in both strains of mice. The ethanol-induced increase in beta-EP release by the hypothalamus of the C57BL/6 mice was more pronounced and longer lasting than that by the hypothalamus of the DBA/2 mice. Similar to beta-EP, an immediate sharp increase of corticotropin-releasing hormone (CRH) release was induced by ethanol which, however, did not present a spike but was maintained significantly higher than spontaneous release for the duration of ethanol exposure. Both ethanol-induced beta-EP and CRH release returned to basal levels within 10 min following removal of ethanol. That beta-EP levels did not remain elevated for the duration of ethanol exposure was not due to tissue depletion of releasable beta-EP pool, since exposure of the hypothalami to 10(-8) M CRH for 10 min, immediately after the perifusion with 20 mM ethanol, resulted in a large increase of beta-EP release. A second ethanol exposure 30 min after the first one did not induce an increase in beta-EP release. However, when the recovery period from the first ethanol exposure was extended to 60 min, a significant increase in the release of hypothalamic beta-EP was observed from the hypothalamus of the C57BL/6 but not of the DBA/2 mice. It is concluded that hypothalamic endorphinergic neurons present a fast, transient increase of beta-EP release in the presence of 20 mM ethanol, and become insensitive to subsequent ethanol exposures for a period of about 60 min. In addition, genetically determined differences exist with regards to the magnitude and duration of the ethanol-stimulated release of beta-EP, as well as on the length of the ethanol nonresponsive period. These differences may explain in part the differences in the voluntary ethanol consumption exhibited by these strains of mice.
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PMID:Effects of single and repeated exposures to ethanol on hypothalamic beta-endorphin and CRH release by the C57BL/6 and DBA/2 strains of mice. 836 33

We investigated the endogenous opioid system and its role in mediating the reinforcing effects of ethanol that lead to high ethanol consumption as a biochemical marker of an individual's vulnerability to excessive ethanol consumption. We performed studies using human subjects with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism to supplement our studies with experimental animals bred selectively for high- or low-ethanol consumption. HR subjects had lower basal plasma beta-endorphin levels as compared with LR subjects, but they had a more pronounced release of beta-endorphin after exposure to ethanol. Findings from animal studies indicated that ethanol-preferring (C57BL/6) mice (analogous to the HR human subjects) had higher levels of hypothalamic beta-endorphin activity than did ethanol-avoiding (DBA/2) mice (analogous to the LR human subjects) under basal conditions. However, the C57BL/6 mice had a more pronounced release of hypothalamic beta-endorphin than did DBA/2 mice after exposure to ethanol. Thus, although hypothalamic beta-endorphin system activity in human and animal models of alcoholism differs under basal conditions, there is enhanced hypothalamic beta-endorphin system activity after exposure to ethanol in both models. We have also performed studies comparing the density and distribution of opioid receptors in brains of ethanol-preferring animals, such as C57BL/6 mice and ALKO-alcohol (AA) rats, and ethanol-avoiding animals, such as DBA/2 mice and ALKO-non-alcohol (ANA) rats. Interestingly, it was observed that in distinct brain regions known to be important for mediating the process of reinforcement, the C57BL/6 mice had a higher density of delta-opioid receptors than the DBA/2 mice, while the AA rats had a higher density of mu-opioid receptors than the ANA rats. Thus, in the ethanol-preferring animals, the increased release of beta-endorphin following exposure to ethanol was associated with a higher density of delta- or mu-opioid receptors in brain regions important for reinforcement, such as the nucleus accumbens and the ventral tegmental area, and may interact with the dopaminergic system and promote ethanol's reinforcing properties, leading to excessive drinking and alcoholism.
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PMID:Implications of endogenous opioids and dopamine in alcoholism: human and basic science studies. 873 99

Genetically determined differences in the activity of the hypothalamic beta-endorphin system have been demonstrated between the C57BL/6 (alcohol-preferring) and DBA/2 (alcohol-aversive) inbred strains of mice. The present studies examined the distribution and density of the mu and delta receptors in specific brain regions that may mediate the rewarding and reinforcing effects of ethanol, using quantitative autoradiography and the specific mu agonist FK 33-824 and delta agonist DPDPE, in their iodinated form. 125I-FK 33-824 recognizes a high affinity binding site in brain membrane preparations from both the C57BL/6 (Kd = 1.37 +/- 0.22 nM; Bmax = 80 +/- 12.3 fmol/mg protein) and DBA/2 mice (Kd = 1.02 +/- 0.16 nM; Bmax = 39.5 +/- 9.6 fmol/mg protein), whereas 125I-DPDPE binds to a high affinity binding site in brain membranes from both the C57BL/6 (Kd = 1.08 +/- 0.34 nM; Bmax = 24.4 +/- 4.5 fmol/mg protein) and DBA/2 mice (Kd = 0.68 +/- 0.24 nM; Bmax = 15.3 +/- 3.7 fmol/mg protein). The autoradiographic studies demonstrated differences in the density of the mu opioid receptors between the two strains of mice in brain nuclei that are not directly related to the brain reward system. However, strain-related differences in the density of delta opioid receptors were observed in regions of the limbic system known to mediate the positive reinforcing effects of many drugs of abuse. The density of delta receptors was significantly higher in the ventral tegmental area and nucleus accumbens of the C57BL/6 mice. The results of the present study support the hypothesis that genetically determined differences exist in the density of opioid receptors in distinct regions of the brain between the C57BL/6 and DBA/2 inbred strains of mice, which may play a role in controlling their voluntary ethanol consumption.
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PMID:Characterization of the mu and delta opioid receptors in the brain of the C57BL/6 and DBA/2 mice, selected for their differences in voluntary ethanol consumption. 919 36

We investigated the endogenous opioid system and its role in mediating the reinforcing effects of ethanol that lead to high ethanol consumption as a biochemical marker of an individual's vulnerability to excessive ethanol consumption. We performed studies using human subjects with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism to supplement our studies with experimental animals bred selectively for high- or low-ethanol consumption. HR subjects had lower basal plasma beta-endorphin levels as compared with LR subjects, but they had a more pronounced release of beta-endorphin after exposure to ethanol. Findings from animal studies indicated that ethanol-preferring (C57BL/6) mice (analogous to the HR human subjects) had higher levels of hypothalamic beta-endorphin activity than did ethanol-avoiding (DBA/2) mice (analogous to the LR human subjects) under basal conditions. However, the C57BL/6 mice had a more pronounced release of hypothalamic beta-endorphin than did DBA/2 mice after exposure to ethanol. Thus, although hypothalamic beta-endorphin system activity in human and animal models of alcoholism differs under basal conditions, there is enhanced hypothalamic beta-endorphin system activity after exposure to ethanol in both models. We have also performed studies comparing the density and distribution of opioid receptors in brains of ethanol-preferring animals, such as C57BL/6 mice and ALKO-alcohol (AA) rats, and ethanol-avoiding animals, such as DBA/2 mice and ALKO-non-alcohol (ANA) rats. Interestingly, it was observed that in distinct brain regions known to be important for mediating the process of reinforcement, the C57BL/6 mice had a higher density of delta-opioid receptors than the DBA/2 mice, while the AA rats had a higher density of mu-opioid receptors than the ANA rats. Thus, in the ethanol-preferring animals, the increased release of beta-endorphin following exposure to ethanol was associated with a higher density of delta- or mu-opioid receptors in brain regions important for reinforcement, such as the nucleus accumbens and the ventral tegmental area, and may interact with the dopaminergic system and promote ethanol's reinforcing properties, leading to excessive drinking and alcoholism.
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PMID:Implications of endogenous opioids and dopamine in alcoholism: human and basic science studies. 984 36

Differences in the activity of distinct components of the endogenous opioid system between ethanol-preferring and ethanol-avoiding animals may be important in controlling their voluntary alcohol consumption. The objective of the present studies was to compare the activity of two opioid peptide systems (enkephalin and beta-endorphin) in distinct regions of the brain, between the C57BL/6 and DBA/2 mice, using sensitive radioimmunoassays, in situ hybridization, and immunohistochemical techniques. The immunohistochemical studies indicated that there was no significant difference in the number of either beta-endorphin or enkephalin immunopositive cells between the C57BL/6 and DBA/2 mice. The in situ hybridization studies demonstrated a 27% higher content of proopiomelanocortin mRNA in the arcuate nucleus of the C57BL/6 than DBA/2 mice, p < 0.02. The content of proenkephalin mRNA was 25% higher in the nucleus accumbens, p < 0.005 and 23% higher in the caudate putamen, p < 0.01, of the C57BL/6 than DBA/2 mice. There was no significant difference in the content of beta-endorphin peptides in the distinct brain regions investigated. The content of met-enkephalin-arg6-phe7 in the nucleus accumbens and caudate was similar between the two strains of mice, while it was significantly lower in the amygdala, hippocampus, ventral tegmental area, and periaqueductal grey of the C57BL/6 than DBA/2 mice. Thus, there are significant differences in the activity of these two endogenous opioid peptide systems in distinct regions of the brain, between ethanol naive C57BL/6 and DBA/2 mice, which may play a role in controlling their alcohol consumption.
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PMID:Comparison of the proopiomelanocortin and proenkephalin opioid peptide systems in brain regions of the alcohol-preferring C57BL/6 and alcohol-avoiding DBA/2 mice. 1045 70

Fusion of mouse peritoneal macrophages or human blood monocytes with weakly metastatic mouse Cloudman S91 melanoma cells resulted in hybrids with enhanced metastatic potential (Rachkovsky et al., 1998. Clin. Exp. Metastasis, 16: 299-312). With few exceptions, such hybrids also showed increased basal- and MSH-induced pigmentation, at least in part through increased N-glycosylation of melanogenic proteins (Sodi et al., 1998. Pigment Cell Res., 11: 299-309). Here we report analyses regarding expression of the melanocyte-stimulating hormone (MSH) receptor (melanocortin-1 receptor, MC1-R) and the melanogenic proteins, tyrosinase (E.C. 1.14.18.1), tyrosinase-related protein 1 (TRP-1), and the tyrosinase-related protein 2 (TRP-2, E.C. 5.3.2.3), by a panel of cell lines consisting of parental Cloudman S91 melanoma cells, macrophages from DBA/2J mice, artificially derived macrophage x melanoma hybrids of high and low metastatic potential, and a naturally occurring highly metastatic hybrid between a Cloudman S91 tumor cell and a DBA/2J tumor-infiltrating cell. We show that incubation of cells with MSH/isobutylmethylxanthine (IBMX) resulted in strong melanogenic and morphologic responses in high metastatic hybrids compared to parental cells and the low metastatic hybrid, and that high metastatic hybrids exhibit increased mRNA expression for MC1-R accompanied by increased 125I-alphaMSH binding. Although tyrosinase activity and the protein level for tyrosinase and TRP-2, but not for TRP-1, were increased in the high metastatic hybrids versus the other cells, no significant changes in mRNA either for tyrosinase or for TRPs were observed in them. Furthermore, unlike tyrosinase, the abundance and gel mobility pattern of TRP-2 did not correlate with changes in activity in all hybrids and parental melanoma cells. The results suggest that although the activity MC1-R and tyrosinase correlate with enhanced basal as well as MSH-induced melanogenesis in metastatic/melanotic hybrids, their expression is differentially regulated, i.e., regulation of MC1-R while at transcriptional level, the TRPs are primarily regulated via post-transcriptional mechanisms in high metastatic hybrids.
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PMID:Upregulation of mRNA for the melanocortin-1 receptor but not for melanogenic proteins in macrophage x melanoma fusion hybrids exhibiting increased melanogenic and metastatic potential. 1061 75

Complex behaviors such as those associated with reward to unconditioned positive reinforcers are polygenic processes. In studies using genetically modified mice specific for the endogenous opioid systems an observed phenotype in a complex behavior is likely to be dependent on interacting genes which, in inbred mouse lines, influence that phenotype. To address this issue we examined operant responding for palatable food reinforcers in mice lacking the expression of beta-endorphin, enkephalin or both peptides congenic to two different genetic backgrounds; C57BL/6J and DBA/2J. These two inbred strains were chosen because their endogenous opioid states differ and they respond differently to exogenous opioids in many behavioral assays. We found that wildtype and mutant C57BL/6J mice acquired operant responding for food reinforcers faster than DBA/2J mice, regardless of their opioid genotype. Although wildtype DBA/2J mice had a significant deficit in acquisition of bar-pressing behavior to reach a pre-established performance criterion, no subsequent deficit was observed under two different schedules of reinforcement. Additionally, we found that mice lacking enkephalin had decreased motivation to bar press for palatable food reinforcers under a progressive ratio regardless of sex or background strain. In contrast, the only subset of beta-endorphin-deficient mice that had decreased motivation to bar press under a progressive ratio was males on the C57BL/6J background. Of the two classical endogenous opioid peptides with preferential activation of the mu opioid receptor, the knockout models would suggest that enkephalins play a more consistent role than beta-endorphin in mediating the motivation for food reward when tested under a progressive ratio.
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PMID:The contribution of endogenous opioids to food reward is dependent on sex and background strain. 1704 74

The study of genetic variance in opioid receptor antagonism of sucrose and other forms of sweet intake has been limited to reductions in sweet intake in mice that are opioid receptor-deficient or lacking either pre-pro-enkephalin or beta-endorphin. Marked genetic variance in inbred mouse strains has been observed for sucrose intake across a wide array of concentrations in terms of sensitivity, magnitude, percentages of kilocalories consumed as sucrose and compensatory chow intake. The present study examined potential genetic variance in systemic naltrexone's dose-dependent (0.01-5 mg/kg) and time-dependent (5-120 min) ability to decrease sucrose (10%) intake in eleven inbred (A/J, AKR/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, SJL/J, SWR/J, 129P3/J) and one outbred (CD-1) mouse strains. A minimum criterion sucrose intake (1 ml) under vehicle treatment, designed to avoid "floor effects" of antagonist treatment was not achieved in three (A/J, AKR/J, CBA/J) inbred mouse strains. Marked genetic variance in naltrexone's ability to inhibit sucrose intake was observed in the remaining strains with the greatest sensitivity observed in the C57BL/10J and C57BL/6J strains, intermediate sensitivity in BALB/cJ, C3H/HeJ, CD-1 and DBA/2J mice, and the least sensitivity in 129P3/J, SWR/J and SJL/J strains with a 7.5-36.5 fold range of greater effects in the ID(50) of naltrexone-induced inhibition in C57BL/10J relative to the three less-sensitive strains across the time course. Naltrexone primarily affected the maintenance, rather than the initiation of intake in BALB/cJ, CD-1, C3H/HeJ, DBA/2J and SJL/J mice, but significantly reduced sucrose intake at higher doses across the time course in C57BL/6J, C57BL/10J and 129P3/J mice. Whereas SWR/J mice failed to display any significant reduction in sucrose intake at any time point following any of the naltrexone doses, naltrexone's maximal magnitude of inhibitory effects was small (35-40%) in 129P3/J and SJL/J mice, moderate ( approximately 50%) in BALB/cJ, C3H/HeJ, CD-1 and DBA2/J mice, and profound (70-80%) in C57BL/6J and C57BL/10J mice. Indeed, the latter two strains displayed significantly greater percentages of naltrexone-induced inhibition of sucrose intake than virtually all other strains. These data indicate the importance of genetic variability in opioid modulation of sucrose intake.
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PMID:Genetic variance contributes to naltrexone-induced inhibition of sucrose intake in inbred and outbred mouse strains. 1720 54


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