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)

Dexfenfluramine (d-FF) and opiate agonists both act on food intake but in opposite ways. Serotonin is known to be involved in the pharmacological action of both d-FF and opiates, but not necessarily in the feeding effect of the latter. In order to test this hypothesis, the effects of three opioid agonists, beta-endorphin, dynorphin and D-Ser2-Leu-Enk-Thr6 (DSLET) and of an antagonist, naltrexone, were investigated individually and in combination with d-FF on food intake and brain serotonin turnover. The opioid agonist-d-FF combinations generally produced a similar anorectic effect to that of d-FF alone, with the exception of DSLET which showed a reciprocal antagonism. The serotonergic effects varied according to the opioid tested, alone or in combination with d-FF. This does not allow to highlight a general pattern of serotonin involvement in the feeding effects of these peptides. However, all the treatments which decreased feeding (d-FF, naltrexone and the combinations dynorphin-d-FF and beta-endorphin-d-FF) displayed similar trends in hypothalamic serotonergic variations. This study evidences a role of serotonin in the feeding effect of opiates, although not similar for all of them. The use of d-FF provides a tool for assessing this involvement.
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PMID:Effects of dexfenfluramine and opioid peptides, alone or in combination, on food intake and brain serotonin turnover in rats. 167 25

Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.
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PMID:Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women. 206 May 60

D-Fenfluramine, an anorectic that releases serotonin (5-HT), repeatedly injected in rats (15 mg/kg per day) enhanced the met5-enkephalin and beta-endorphin content of the hyhpothalamus. The onset of this effect was slow, reaching a peak at 5 days; the increase in beta-endorphin gradually declined toward control level while the drug was still being administered although that of met-enkephalin persisted for 15 days. The elevation of the opioid peptide content of the hypothalamus was temporally associated with a slowing in the rate of body weight increase. A transient, small, increase in striatal met-enkephalin content was also induced by repeated D-fenfluramine injections; however the met-enkephalin content of frontal cortex, hippocampus and brainstem was not affected. A modification of the beta-endorphin content of hypothalamus was not seen after acute injection of D-fenfluramine or D-amphetamine but an increase was observed during repeated treatment with D-fenfluramine. Repeated injections of D-amphetamine for 5 days (4.5 mg/kg per day) failed to increase either the met-enkephalin or the beta-endorphin content of the hypothalamus. These data suggest that the anorexia elicited by repeated injections of D-fenfluramine but not that elicited by D-amphetamine, includes a participation by hypothalamic and beta-endorphin stores.
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PMID:Elevation of Met5-enkephalin and beta-endorphin hypothalamic content in rats receiving anorectic drugs: differences between D-fenfluramine and D-amphetamine. 627 58

D-Fenfluramine (D-Fen) increases serotonin (5-HT) content in the synaptic cleft and exerts anorexigenic effects in animals and humans. However, the neural circuits that mediate these effects are not fully identified. To address this issue, we assessed the efficacy of D-Fen-induced hypophagia in mouse models with manipulations of several genes in selective populations of neurons. Expectedly, we found that global deletion of 5-HT 2C receptors (5-HT(2C)Rs) significantly attenuated D-Fen-induced anorexia. These anorexigenic effects were restored in mice with 5-HT(2C)Rs expressed only in pro-opiomelanocortin (POMC) neurons. Further, we found that deletion of melanocortin 4 receptors (MC4Rs), a downstream target of POMC neurons, abolished anorexigenic effects of D-Fen. Reexpression of MC4Rs only in SIM1 neurons in the hypothalamic paraventricular nucleus and neurons in the amygdala was sufficient to restore the hypophagic property of D-Fen. Thus, our results identify a neurochemically defined neural circuit through which D-Fen influences appetite and thereby indicate that this 5-HT(2C)R/POMC-MC4R/SIM1 circuit may yield a more refined target to exploit for weight loss.
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PMID:A serotonin and melanocortin circuit mediates D-fenfluramine anorexia. 2104 20