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)

Two anorectic drugs which stimulate serotonin neuronal activity by releasing serotonin from nerve terminals, d-fenfluramine and CM 57 277 (4-amino-[6-chloro-2-pyridyl]-1-piperidine HCl), were studied in rats. Both drugs, when given for 5 days at doses of 15 mg of d-fenfluramine per kg/day and 20 mg of CM 57 277 per kg/day, decreased body weight gain and increased content of Met5-enkephalin and beta-endorphin in hypothalamus, but not in frontal cortex or pituitary. The increase in the hypothalamic content of the two opioid peptides elicited by d-fenfluramine was reversed by metergoline and p-chlorophenylalanine, suggesting that it is mediated by serotonin. The content of two other hypothalamic neuropeptides, cholecystokinin and substance P, were not affected by d-fenfluramine. Although Met5-enkephalin content in striatum was increased transiently by d-fenfluramine, this was not a serotonin-mediated effect because it was not abolished by metergoline. The decrease in body weight gain was prevented by metergoline, but not by i.p. injection of p-chlorophenylalanine. The effect of p-chlorophenylalanine on intestine may contribute to its failure in reversing the anorectic effect of d-fenfluramine. Naltrexone, an antagonist of opiate receptor, decreased body weight gain but exerted no effect on hypothalamic Met5-enkephalin or beta-endorphin content. Taking into consideration that the increase in Met5-enkephalin and beta-endorphin may have resulted from accumulation due to decreased utilization, the anorectic effects of serotonin releasing drugs may be mediated by a reduction in the functional role of hypothalamic opioid peptides.
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PMID:Accumulation of hypothalamic endorphins after repeated injections of anorectics which release serotonin. 629 96

The present study examined the effects of the 5-hydroxytryptaminergic (5HT)2/1c agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on periventricular-hypophysial dopaminergic (DA) neuronal activity and the secretion of alpha-melanocyte-stimulating hormone (alpha MSH). For comparison, the effects of DOI on tuberoinfundibular DA neuronal activity and the secretion of prolactin were also examined. Periventricular hypophysial and tuberoinfundibular DA neuronal activities were estimated by measuring the concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the terminal regions of these neurons; i.e., in the intermediate lobe of the pituitary and median eminence, respectively. Acute administration of DOI produced dose- and time-related decreases in intermediate lobe DOPAC concentrations and corresponding increases in plasma alpha MSH concentrations. Pretreatment of animals with either the 5HT2/1c antagonist ritanserin or the selective 5HT2 antagonist alpha-phenyl-1-(2-phenylethyl)-4-piperidine methanol (MDL-11,939) blocked the DOI-induced decrease in intermediate lobe DOPAC concentrations and increase in plasma alpha MSH concentrations. Acute administration of DOI produced dose- and time-related increases in plasma prolactin concentrations but did not alter DOPAC concentrations in the median eminence. Furthermore, the DOI-induced increase in plasma prolactin concentrations was blocked by ritanserin, but not MDL-11,939 pretreatment. Taken together, these data suggest that DOI inhibits periventricular hypophysial DA neuronal activity and increases the secretion of alpha MSH by activating 5HT2 receptors, whereas the DOI-induced prolactin secretion is independent of a decrease in tuberoinfundibular DA neuronal activity and is most likely mediated by 5HT2/1c receptor activation.
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PMID:5-Hydroxytryptamine2 receptor-mediated regulation of periventricular-hypophysial dopaminergic neuronal activity and the secretion of alpha-melanocyte-stimulating hormone. 830 54

The effect of acetylcholine on the neurointermediate lobe beta-endorphin secretion was studied in the neonatal and in the adult rat in vitro. Acetylcholine stimulated beta-endorphin secretion from the 2-day- and 5-day-old neurointermediate lobe, the effect was dose dependent and more pronounced in the presence of the cholinesterase inhibitor eserine. The 10-day-, the 21-day-old and the adult rat neurointermediate lobes did not respond to acetylcholine, even in the presence of eserine. Basal beta-endorphin secretion was elevated by the D2 receptor antagonist sulpiride, but acetylcholine was without effect in the 10-day-old and in the adult neurointermediate lobe even after dopamine receptor blockade. The beta-endorphin stimulatory response to acetylcholine was diminished by the M1 muscarinic receptor antagonist pirenzepine and blocked by the M3 > M1 antagonist 4-diamino-phenyl-piperidine (4-DAMP). The selective M2 antagonist methoctramine and nicotine had no effect. These data indicate that the neurointermediate lobe beta-endorphin secretion is under special muscarinic cholinergic regulation for a relatively short time after birth. The disappearance of this stimulatory cholinergic effect in later life might be due to changes in the intracellular secretory machinery in the IL and/or to the uncoupling of the cholinergic receptors from the intracellular signal transduction system(s) responsible for the stimulated secretion in the rat melanotrope cells.
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PMID:Age-dependent muscarinic stimulation of beta-endorphin secretion from rat neurointermediate lobe in vitro. 942 Nov 36

Phencyclidine (PCP) activates the hypothalamo-pituitary-adrenal (HPA) axis and decreases plasma prolactin levels in the rat. PCP is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, but it also inhibits the reuptake of dopamine, serotonin and norepinephrine. The purpose of the present study was to utilize the PCP analogue N-[1-(2-thienyl)cyclohexyl]piperidine; (TCP), the potent dopamine reuptake inhibitor N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine; (BTCP) and the nonselective monoamine reuptake inhibitor cocaine as pharmacologic probes in order to determine the roles of noncompetitive NMDA receptor blockade and inhibition of dopamine reuptake in the neuroendocrine effects of PCP. PCP, TCP and cocaine increased plasma levels of adrenocorticotropin and corticosterone, but BTCP had no effect. In contrast, PCP, BTCP and cocaine decreased plasma prolactin, but TCP produced no such effect. The data suggest that mechanisms besides inhibition of dopamine reuptake are involved in the effects of PCP on the HPA axis, and the PCP-induced decrease in plasma prolactin is not a consequence of inhibition of NMDA receptor-mediated neurotransmission.
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PMID:The role of antagonism of NMDA receptor-mediated neurotransmission and inhibition of the dopamine reuptake in the neuroendocrine effects of phencyclidine. 1628 27

The melanocortin system is an important treatment target towards improving both adiposity (excessive body fat) and adiposopathy (dysfunctional body fat). Melanocortin agonism can be achieved by increasing CNS leptin and/or insulin activity, which is dependent upon peripheral leptin/insulin production, transport across the blood-brain barrier (potentially relevant to inhaled/nasal insulin), and effects upon CNS target receptors. Melanocortin agonism may also be achieved through inhibiting inverse agonists of melanocortin receptors (such as inhibition of agouti-related peptide), and directly through selective melanocortin receptor ligands such as piperazine, piperidine, pyridazinone, tetrahydropyran, thiadiazole and diazole derivatives. While the development of most (but not all) neuropeptide Y inhibitors as monotherapy interventions have demonstrated limited efficacy thus far, it is possible that the combination of a neuropeptide Y inhibitor with a selective melanocortin receptor ligand may provide improved weight loss over that of either agent alone. In general, melanocortin system agonism promotes weight loss through decreasing appetite, increasing sympathetic nervous system activity, and modulating thyroid-releasing hormone, corticotropin-releasing hormone, brain-derived neurotrophic factor, melanin-concentrating hormone and orexin. Of particular interest, given the development of cannabinoid receptor antagonists as weight loss agents, is the fact that receptors in the endocannabinoid system are also affected by the melanocortin system. It will only be through the conduct of human clinical trials that melanocortin agonists will be proven to reduce adiposity to a meaningful degree, and, as importantly, be proven to improve adiposopathy, and thus effectively treat excessive fat-related metabolic diseases.
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PMID:The melanocortin system as a therapeutic treatment target for adiposity and adiposopathy. 1692 90