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)

Antisera (AS) raised against rat melanin-concentrating hormone (rMCH) and against two additional peptides sequences derived from the rat MCH precursor (neuropeptide glutamic acid-isoleucineamide (NEI), and neuropeptide glycine-glutamic acid (NGE)) exclusively stained the hypothalamic neurons previously described using AS to salmon MCH, human somatocrinin 1-37 (GRF37) and alpha-MSH. Liquid phase and dot-blot controls for specificity indicated that rMCH-, NEI- and NGE-AS bound epitopes recognized by sMCH-, alpha-MSH- and GRF-37-AS, respectively. The distinct intracellular patterns of immunoreactivity obtained in control animals with rMCH-, NGE- and NEI-AS, as well as the changes observed after intracerebroventricular injection of colchicine matched previous findings using sMCH-, GRF37- and alpha-MSH-AS.
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PMID:Immunoreactivities for antisera to three putative neuropeptides of the rat melanin-concentrating hormone precursor are coexpressed in neurons of the rat lateral dorsal hypothalamus. 164 Nov 82

1. The darkening actions of MCH (melanin concentrating hormone), alpha-MSH and the synthetic analog [Nle4, D-Phe7]-alpha-MSH on the toad, Bufo ictericus ictericus, melanophores were studied regarding the role of calcium in the hormone receptor coupling, signal transduction and intracellular pigment translocation. 2. In the absence of external calcium, MCH and both melanotropins still elicit maximal skin darkening. 3. Verapamil, a calcium-channel blocker, completely abolishes the alpha-MSH-induced response and partially inhibits MCH-induced darkening, although the calcium carrier, ionophore A23187, was unable to promote any pigment translocation. 4. Since darkening responses promoted by cyclic nucleotides proceeded normally in the presence of verapamil and extracellular calcium was not necessary for melanotropin dispersing action, it is suggested that the blocking activity obtained with verapamil is probably due to an impairment of the Ca2+-dependent adenylate cyclase activity. 5. Reversal of melanotropin-induced darkening could be obtained with melatonin, in both normal and Ca2+-free Ringer, whereas MCH darkening is reversed by melatonin only in the absence of calcium. 6. The results seem to indicate that calcium is not required for hormone receptor binding and pigment migration, whereas it is specifically needed for signal transduction.
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PMID:alpha-MSH (melanocyte stimulating hormone) and MCH (melanin concentrating hormone) actions in Bufo ictericus ictericus melanophores. 288 67

Coexistence of MCH- and alpha-MSH-like peptides in specific neurons of the frog hypothalamus has been investigated on serial frozen sections using the indirect immunofluorescence method. In the anterior region of the preoptic nucleus, perikarya containing MCH- and alpha-MSH-immunoreactive materials were co-distributed and the two peptides were generally co-sequestered within the same neurons. In contrast, alpha-MSH immunoreactive neurons of the ventral infundibular nucleus did not contain any MCH-like peptide. These data suggest that MCH and alpha-MSH are transported by the same nerve fibers originating from preoptic perikarya and are likely released together by axon terminals. Since MCH and alpha-MSH exert antagonistic hormonal activities on dermal melanophores, our results suggest that the two regulatory peptides may also interact in the central nervous system.
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PMID:Coexistence of melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in the preoptic nucleus of the frog brain. 355 29

The peptides alpha-melanocyte stimulating hormone (alpha-MSH) and melanin concentrating hormone (MCH; rat and salmon sequence) were administered to anesthetized rats by intracerebroventricular infusion. Depth recordings were carried out in the dorsal hippocampus, and auditory gating was assessed. Auditory gating in this paradigm refers to the decrease in amplitude of the second of two tone-evoked CNS potentials that can be measured when pairs of identical tones are presented 500 ms apart. Alpha-MSH increases auditory gating, whereas MCH has the opposite effect. When MCH was administered prior to alpha-MSH, the ability of alpha-MSH to increase auditory gating was blocked. Thus, the two peptides appear to be functional antagonists.
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PMID:Alpha-MSH and MCH are functional antagonists in a CNS auditory gating paradigm. 839 16

The behavioral effects of alpha-MSH, MCH, and alpha-MSH + MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) (bilateral, 100 ng in 0.5 microliter). Infusion of alpha-MSH into the VMN increased aggressive behavior; in the MPOA it reduced exploration and increased anxiety. In both areas it stimulated sexual behavior. MCH also stimulated sexual behavior in the MPOA and VMN and had an anxiogenic effect in the MPOA. The effect of alpha-MSH on aggression and exploration was antagonized by MCH. When given together, the two peptides were mutually antagonistic on anxiety. This study indicates that MCH has central nervous system effects and may be a partial alpha-MSH agonist.
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PMID:Behavioral effects of alpha-MSH and MCH after central administration in the female rat. 882 27

The behavioral and neurochemical effects of NEI, and its interaction with alpha-MSH or MCH were investigated in the ventromedial nucleus (VMN) and medial preoptic area (MPOA) in female rats (bilateral administration, 100 ng in 0.5 microliter/side). NEI in the VMN (but not in the MPOA) stimulated exploratory behavior, increased anxiety and reduced dopamine and DOPAC release. The behavioral effects were antagonized by alpha-MSH. NEI stimulated female sexual receptivity in the MPOA. In the VMN, NEI did not have any effect on sexual activity, but partially antagonized the stimulatory effect of MCH. These results show that NEI in the hypothalamus participates in the regulation of behavior, possibly through dopaminergic mediation.
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PMID:Behavioral effects of neuropeptide E-I (NEI) in the female rat: interactions with alpha-MSH, MCH and dopamine. 970 Jul 48

A photoreactive analogue of human melanin-concentrating hormone was designed, [D-Bpa13,Tyr19-MCH, containing the D-enantiomer of photolabile p-benzoylphenylalanine (Bpa) in position 13 and tyrosine for radioiodination in position 19. The linear peptide was synthesized by the continuous-flow solid-phase methodology using Fmoc-strategy and PEG-PS resins, purified to homogeneity and cyclized by iodine oxidation. Radioiodination of [D-Bpa13,Tyr19]-MCH at its Tyr19 residue was carried out enzymatically using solid-phase bound glucose oxidase/lactoperoxidase, followed by purification on a reversed-phase mini-column and HPLC. Saturation binding analysis of [125I]-[D-Bpa13,Tyr19]-MCH with G4F-7 mouse melanoma cells gave a K(D) of 2.2+/-0.2 x 10(-10) mol/l and a B(max) of 1047+/-50 receptors/cell. Competition binding analysis showed that MCH and rANF(1-28) displace [125I]-[D-Bpa13,Tyr19]-MCH from the MCH binding sites on G4F-7 cells whereas alpha-MSH has no effect. Receptor crosslinking by UV-irradiation of G4F-7 cells in the presence of [125I]-[D-Bpa13,Tyr19]-MCH followed by SDS-polyacrylamide gel electrophoresis and autoradiography yielded a band of 45-50 kDa. Identical crosslinked bands were also detected in B16-F1 and G4F mouse melanoma cells, in RE and D10 human melanoma cells as well as in COS-7 cells. Weak staining was found in rat PC12 phaeochromocytoma and Chinese hamster ovary cells. No crosslinking was detected in human MP fibroblasts. These data demonstrate that [125I]-[D-Bpa13,Tyr19]-MCH is a versatile photocrosslinking analogue of MCH suitable to identify MCH receptors in different cells and tissues; the MCH receptor in these cells appears to have the size of a G protein-coupled receptor, most likely with a varying degree of glycosylation.
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PMID:(D-(p-benzoylphenylalanine)13, tyrosine19)-melanin-concentrating hormone, a potent analogue for MCH receptor crosslinking. 1036 6

It is known that alpha-MSH augments cAMP levels in rat brain slices containing accumbens and caudate-putamen nuclei. In this study we examined: a) the effect of other neuropeptides: MCH and NEI, on this cyclic nucleotide; b) if the effects of alpha-MSH on cAMP production can be modulated by addition of MCH or NEI to the incubation medium. Both MCH and NEI (3.6 microM) increased the production of cAMP, whereas at doses of 0.6 microM exerted no effects. When alpha-MSH 0.6 microM was added with NEI or MCH (0.6 microM), only MCH blocked the increase in the cAMP induced by alpha-MSH. Neither MCH nor NEI at the highest dose used (3.6 microM) had any additive effect on AMPc when added together with alpha-MSH. We conclude that, at a high concentration, (MCH/NEI)-like peptides can use the intracellular signal transduction linked to cyclic nucleotides in the CNS.
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PMID:Effects and interactions between alpha-MSH and MCH/NEI upon striatal cAMP levels. 1046 13

A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. Leptin, a hormone secreted by fat cells, acts in rodents via hypothalamic receptors to inhibit feeding and increase thermogenesis. A feedback regulatory loop with three distinct steps has been identified: (1) a sensor (leptin production by adipose cells) monitors the size of the adipose tissue mass; (2) hypothalamic centers receive and integrate the intensity of the leptin signal through leptin receptors (LRb); (3) effector systems, including the sympathetic nervous system, control the two main determinants of energy balance-energy intake and energy expenditure. While this feedback regulatory loop is well established in rodents, there are many unsolved questions about its applicability to body weight regulation in humans. The rate of leptin production is related to adiposity, but a large portion of the interindividual variability in plasma leptin concentration is independent of body fatness. Gender is an important factor determining plasma leptin, with women having markedly higher leptin concentrations than men for any given degree of fat mass. The ob mRNA expression is also upregulated by glucocorticoids, whereas stimulation of the sympathetic nervous system results in its inhibition. Furthermore, leptin is not a satiety factor in humans because changes in food intake do not induce short-term increases in plasma leptin levels. After its binding to LRb in the hypothalamus, leptin stimulates a specific signaling cascade that results in the inhibition of several orexigenic neuropeptides, while stimulating several anorexigenic peptides. The orexigenic neuropeptides that are downregulated by leptin are NPY (neuropeptide Y), MCH (melanin-concentrating hormone), orexins, and AGRP (agouti-related peptide). The anorexigenic neuropeptides that are upregulated by leptin are alpha-MSH (alpha-melanocyte-stimulating hormone), which acts on MC4R (melanocortin-4 receptor); CART (cocaine and amphetamine-regulated transcript); and CRH (corticotropin-releasing-hormone). Obese humans have high plasma leptin concentrations related to the size of adipose tissue, but this elevated leptin signal does not induce the expected responses (i.e., a reduction in food intake and an increase in energy expenditure). This suggests that obese humans are resistant to the effects of endogenous leptin. This resistance is also shown by the lack of effect of exogenous leptin administration to induce weight loss in obese patients. The mechanisms that may account for leptin resistance in human obesity include a limitation of the blood-brain-barrier transport system for leptin and an inhibition of the leptin signaling pathways in leptin-responsive hypothalamic neurons. During periods of energy deficit, the fall in leptin plasma levels exceeds the rate at which fat stores are decreased. Reduction of the leptin signal induces several neuroendocrine responses that tend to limit weight loss, such as hunger, food-seeking behavior, and suppression of plasma thyroid hormone levels. Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.
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PMID:Leptin signaling, adiposity, and energy balance. 1207 65

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.
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PMID:Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance. 1472 56


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