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)

Recent studies have revealed that the brain produces interferon-alpha (IFN-alpha) in response to noninflammatory as well as inflammatory stress and that it might have a role in normal physiology. When administered intracerebrally, IFN-alpha causes diverse effects including fever, anorexia, analgesia and changes in the central neuronal activities. These responses are inhibited by the opioid receptor antagonist naloxone. This is consistent with the reports suggesting that recombinant human (rh) IFN-alpha binds to opioid receptors in rodent brain membrane. We revealed that rhIFN-alpha altered the activity of thermosensitive neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which produces opioid-dependent analgesia is known to suppress the cytotoxicity of splenic natural killer cells, we investigated whether the administration of beta-endorphin and rhIFN-alpha may induce a similar immunosuppression. We found that central, but not peripheral, injection of both compounds inhibited natural killer (NK) cytotoxicity. Further studies revealed that rhIFN-alpha decreased the activity of MPO neurons via opioid receptors and the altered activity of MPO neurons in turn resulted in the activation of corticotropin-releasing factor neurons, thereby suppressing NK cytotoxicity predominantly through activation of the splenic sympathetic nerve and beta-receptor mechanisms in splenocytes. Thus, IFN-alpha may alter the brain activity to exert a feedback effect on the immune system. Further detailed whole-cell clamping analyses on neuronal mechanisms in rat brain tissue slices showed that the inhibitory effect of rhIFN-alpha on N-methyl-D-aspartate-induced membrane current responses of MPO neurons was mediated not only by opioid receptors but also by the local production of reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to neuron-glial cell interaction.
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PMID:Neuroimmunomodulatory actions of hypothalamic interferon-alpha. 973 Jun 83

Adult female Zucker lean and obese rats were treated for 14 days with 3.5 nm/kg oleoyl-estrone (OE) in liposomes (Merlin-2) through continuous i.v. injection with osmotic minipumps. Rat wt. and food intake were measured daily. On days 0, 3, 6, 10, and 14, groups of rats were killed and their hypothalamic nuclei [lateral preoptic (LPO), median preoptic (MPO), paraventricular (PVN), ventromedial (VMH), and arcuate (ARC)] were dissected, homogenized, and used for the measurement of corticosterone-releasing hormone (CRH) by radioimmunoassay. The OE treatment decreased food intake by 67.4% in lean and 62.6% in obese rats (means for 14 days). Body wt. decreased steadily in lean and obese rats, the gap between controls and treated rats becoming 11.5% of initial body wt. in the lean and 12.4% in the obese. The levels of CRH in the ARC nucleus were at least 10-fold higher than in the other nuclei. No changes in CRH were observed in any of the nuclei of obese rats, with levels up to day 6 similar to those of lean rats. In the lean rats, the LPO and ARC nuclei showed peaks on day 10, while the MPO showed no changes and the PVN and VMH nuclei showed a progressive increase, to a maximum at the end of the study (day 14). This contrasted with the peak of plasma adrenocorticotropic hormone (ACTH) and corticosterone (day 6 in lean and day 14 in obese rats). There was a definite lack of correlation between the plasma levels of these two hormones and the levels of CRH in the hypothalamic nuclei, and between the latter and the decreases in appetite in the rats. The loss of appetite induced by OE is not necessarily mediated by CRH, because the obese rats show an intense decrease in voluntary food intake but their hypothalamic nuclei CRH levels do not change at all. Hypothalamic nuclei CRH does not, necessarily, mediate the rise in glucocorticoids induced by OE treatment, because this is observed in lean and obese rats, lean rats increases being mismatched with those of hypothalamic CRH. The OE induced changes in hypothalamic CRH require a fully functional leptinergic pathway, because it is not observed in Zucker fa/fa rats lacking a working leptin receptor. This--indirectly--shows that leptin is needed for its synthesis or modulation.
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PMID:Zucker obese rats are insensitive to the CRH-increasing effect of oleoyl-estrone. 974 90

Neuropeptide Y (NPY) and the endogenous melanocortin receptor antagonist, agouti gene-related protein (AGRP), coexist in the arcuate nucleus, and both exert orexigenic effects. The present study aimed primarily at determining the brain distribution of AGRP. AGRP mRNA-expressing cells were limited to the arcuate nucleus, representing a major subpopulation (95%) of the NPY neurons, which also was confirmed with immunohistochemistry. AGRP-immunoreactive (-ir) terminals all contained NPY and were observed in many brain regions extending from the rostral telencephalon to the pons, including the parabrachial nucleus. NPY-positive, AGRP-negative terminals were observed in many areas. AGRP-ir terminals were reduced dramatically in all brain regions of mice treated neonatally with monosodium glutamate as well as of mice homozygous for the anorexia mutation. Terminals immunoreactive for the melanocortin peptide alpha-melanocyte-stimulating hormone formed a population separate from, but parallel to, the AGRP-ir terminals. Our results show that arcuate NPY neurons, identified by the presence of AGRP, project more extensively in the brain than previously known and indicate that the feeding regulatory actions of NPY may extend beyond the hypothalamus.
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PMID:The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. 984 12

Leptin, the protein product of the obese (ob) gene, has been suggested to play a role in the regulation of food intake. As depressive episodes are frequently characterized by loss of appetite, reduced food intake and weight loss, altered leptin secretion might also be expected in patients with depression. Therefore, we examined nocturnal (10.00 p.m. to 7.00 a.m.) secretion of leptin, cortisol, ACTH and growth hormone (GH) in a group of 15 patients with depression and age- and sex-matched controls (age range 23-71 years). In addition, the effects of pulsatile administration of growth hormone-releasing hormone (GHRH), thought to be an endogenous antagonist of corticotropin-releasing hormone (CRH), which in turn is believed to play a critical role for the pathophysiology of depression, on nocturnal hormone secretion were assessed. Patients with depression showed a trend towards elevated nocturnal cortisol secretion (F = 3.8, p < 0.05). Nocturnal serum leptin was significantly higher in patients, despite a reported weight loss (F = 8, p < 0.05), but showed the same sexual dimorphism as in controls (F = 20.9, p < 0.01). No significant differences were seen between patients and controls with regard to plasma GH and ACTH. GHRH treatment increased GH secretion in both patients and controls, while the other hormones were not affected. Furthermore, serum leptin was correlated with body mass index (BMI) in controls, but not in patients with depression, supporting an altered regulation of leptin secretion in depressive illness. Finally, we provide some evidence that in young female patients the normal nocturnal leptin surge is blunted. As glucocorticoids can prevent the fasting-induced decline in serum leptin, we propose that hypercortisolism in depression might counteract the reduction in leptin secretion caused by decreased food intake and weight loss. Elevated serum leptin in depression might in turn further promote CRH release, as shown in animals and, hence, contribute to HPA system hyperactivity seen in depression.
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PMID:Elevated nocturnal profiles of serum leptin in patients with depression. 984 57

Bacterial-derived products [e.g., lipopolysaccharide (LPS) from Gram-negative and muramyl dipeptide (MDP) from Gram-positive bacteria] are proposed to play a pivotal role in the generation of neurological and neuroinflammatory/immunological responses during bacterial infections of the nervous system. LPS and MDP may act through cytokines; cytokine-neuropeptide interactions may also be involved. Here, we investigated cytokine and neuropeptide mRNA profiles in specific brain regions in response to the intracerebroventricular administration of LPS and MDP. IL-beta1 system components (ligand, signalling receptor, receptor accessory proteins, receptor antagonist), TNF-alpha, TGF-beta1, glycoprotein 130 (IL-6 receptor signal transducer), OB protein (leptin) receptor, neuropeptide Y, Y5 receptor, and pro-opiomelanocortin (opioid peptide precursor) mRNAs were analyzed. The same brain region sample was assayed for all components. LPS and MDP administration induced significantly different behavioral and molecular profiles. LPS was significantly more potent than MDP in inducing anorexia and in up-regulating pro-inflammatory cytokines (IL- beta1 and TNF-alpha mRNAs in the cerebellum, hippocampus and hypothalamus; MDP was more potent in up-regulating anti-inflammatory cytokine (IL-1 receptor antagonist and TGF-beta1) mRNAs. LPS and MDP also modulated hypothalamic IL-1 receptor mRNA components, but did not affect any of the neuropeptide-related components examined. The results suggest that the magnitude of neurological manifestations induced by LPS and MDP may involve the ratio between stimulatory and inhibitory cytokines, and this ratio may have implications for the neuroinflammatory/neurotoxic events associated with bacterial infections of the central nervous system.
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PMID:Gram-negative and gram-positive bacterial products induce differential cytokine profiles in the brain: analysis using an integrative molecular-behavioral in vivo model. 985 41

The voluntary suppression of food intake that accompanies involuntary overfeeding is an effective regulatory response to positive energy balance. Because the pro-opiomelanocortin (POMC)-derived melanocortin system in the hypothalamus promotes anorexia and weight loss and is an important mediator of energy regulation, we hypothesized that it may contribute to the hypophagic response to overfeeding. Two groups of rats were overfed to 105 and 116% of control body weight via a gastric catheter. In the first group, in situ hybridization was used to measure POMC gene expression in the rostral arcuate (ARC). Overfeeding increased POMC mRNA in the ARC by 180% relative to levels in control rats. For rats in the second group, the overfeeding was stopped, and they were infused intracerebroventricularly with SHU9119 (SHU), a melanocortin (MC) antagonist at the MC3 and MC4 receptor, or vehicle. Although SHU (0.1 nmol) had no effect on food intake of control rats, intake of overfed rats increased by 265% relative to CSF-treated controls. This complete reversal of regulatory hypophagia not only maintained but actually increased the already elevated weight of overfed rats, whereas CSF-treated overfed rats lost weight. These results indicate that CNS MCs mediate hypophagic signaling in response to involuntary overfeeding and support the hypothesis that MCs are important in the central control of energy homeostasis.
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PMID:Role of the CNS melanocortin system in the response to overfeeding. 1006 86

We investigated the effects of selective melanocortin MC4 receptor blockage on immobilization stress-induced anorexia. Male rats were subjected to immobilization once a day for 4 days. Prior to each of the stress treatments, the rats were injected i.c.v. (intracerebroventricularly) with either saline or the melanocortin MC4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp-(NH22)2]beta-MSH-(11-22) (melanocyte-stimulating hormone). Rats subjected to neither stress nor i.c.v. injections served as controls. The results showed that the cumulative food intake and body weight gain in the stressed group treated with HS014 was significantly higher than in the stressed group and significantly lower than in the control group. Repeated injections of the melanocortin MC4 receptor antagonist were effective and there were no signs of tachyphylaxis. This is the first report showing that melanocortin MC4 receptor blockage can relieve an anorectic condition, which may indicate that melanocortin MC4 receptor blockage is an effective way to treat anorectic disorders.
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PMID:Selective melanocortin MC4 receptor blockage reduces immobilization stress-induced anorexia in rats. 1020 75

Anorexia nervosa is a syndrome of unknown etiology. It is associated with multiple endocrine abnormalities. Hypothalamic monoamines (especially serotonin), neuropeptides (especially neuropeptide Y and cholecystokinin) and leptin are involved in the regulation of human appetite, and in several ways they are changed in anorexia nervosa. However, it remains to be clarified whether the altered appetite regulation is secondary or etiologic. Increased secretion of corticotropin-releasing hormone and proopiomelanocortin seems to be secondary to starvation, however, there is evidence that it may maintain and intensify anorexia, excessive physical activity and amenorrhea. Hypothalamic amenorrhea, which is a diagnostic criterion in anorexia nervosa, is not solely related to the low body weight and exercise. Growth hormone resistance with low production of insulin-like growth factor I and high growth hormone secretion reflect the nutritional deprivation. The nutritional therapy of patients with anorexia nervosa might be improved by administering an anabolic agent such as growth hormone or insulin-like growth factor I. So far none of the endocrine abnormalities have proved to be primary, however, there is increasing evidence that some of these might participate in a vicious circle.
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PMID:A review of endocrine changes in anorexia nervosa. 1022 46

To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 micrograms) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (-8%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (-15%) and gastrointestinal fill (-50%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin's anorexigenic action.
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PMID:Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat. 1023 36

We have investigated the hormonal and hypothalamic neuropeptidergic substrates of dehydration-associated anorexia. In situ hybridization and hormone analyses of anorexic and paired food-restricted rats revealed two distinct profiles. First, both groups had the characteristic gene expression and endocrine signatures usually associated with starvation: increased neuropeptide Y and decreased proopiomelanocortin and neurotensin mRNAs in the arcuate nucleus (ARH); increased circulating glucocorticoid but reduced leptin and insulin. Dehydrated animals are strongly anorexic despite these attributes, showing that the output of leptin- and insulin-sensitive ARH neurons that ordinarily stimulate eating must be inhibited. The second pattern occurred only in anorexic animals and had two components: (1) reduced corticotropin-releasing hormone (CRH) mRNA in the neuroendocrine paraventricular nucleus (PVH) and (2) increased CRH and neurotensin mRNAs in the lateral hypothalamic (LHA) and retrochiasmatic areas. However, neither corticosterone nor suppressed PVH CRH gene expression is required for anorexia after dehydration because PVH CRH mRNA in dehydrated adrenalectomized animals is unchanged from euhydrated adrenalectomized controls. We also showed that LHA CRH mRNA was strongly correlated with the intensity of anorexia, increased LHA CRH gene expression preceded the onset of anorexia, and dehydrated adrenalectomized animals (which also develop anorexia) had elevated LHA CRH gene expression with a distribution pattern similar to intact animals. Finally, we identified specific efferents from the CRH-containing region of the LHA to the PVH, thereby providing a neuroanatomical framework for the integration by the PVH of neuropeptidergic signals from the ARH and the LHA. Together, these observations suggest that CRH and neurotensin neurons in the LHA constitute a novel anatomical substrate for their well known anorexic effects.
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PMID:Distinct patterns of neuropeptide gene expression in the lateral hypothalamic area and arcuate nucleus are associated with dehydration-induced anorexia. 1040 47


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