Orexin Receptor Type 1 (Hypocretin Receptor Type 1 or HCRTR1) - Orexin receptor type 1 (Ox1R or OX1) is a protein that is encoded by the HCRTR1 gene.

Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

Drug addiction is a chronic illness characterized by high rates of relapse. Relapse to drug use can be triggered by re-exposure to drug-associated cues, stressful events, or the drug itself after a period of abstinence. Pharmacological intervention to reduce the impact of relapse-instigating factors offers a promising target for addiction treatment. Growing evidence has implicated an important role of the orexin/hypocretin system in drug reward and drug-seeking, including animal models of relapse. Here, we review the evidence for the role of orexins in modulating reward and drug-seeking in animal models of addiction and the potential for orexin receptors as specific targets for anti-relapse medication approaches.

Bengtsson MW, Makela K, Herzig KH, Flemstrom G. Short food deprivation inhibits orexin receptor 1 expression and orexin-A induced intracellular calcium signaling in acutely isolated duodenal enterocytes. Am J Physiol Gastrointest Liver Physiol 296: G651-G658, 2009. First published December 31, 2008; doi:10.1152/ajpgi.90387.2008.-Close intra-arterial infusion of the appetite regulating peptide orexin-A stimulates bicarbonate secretion from the duodenal mucosa. The aim of the present study was to elucidate the ability of orexin-A to induce intracellular calcium signaling in acutely isolated duodenal enterocytes. Freshly isolated clusters of enterocytes, obtained from rat duodenal mucosa or human duodenal biopsies, were loaded with fura 2-AM and mounted in a perfusion chamber. Cryptlike enterocytes were selected (caged), and changes in intracellular calcium concentration ([Ca2+](i)) were evaluated by fluorescence imaging. Total RNA was extracted from pellets of enterocytes and reverse transcribed ...

Disrupted sleep is associated with increased risk of type 2 diabetes. Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia. Resting-phase administration of dual orexin receptor antagonist (DORA) has been shown to improve sleep abnormalities and glucose intolerance in type 2 diabetic db/db mice, although the mechanism remains unknown. In the present study, to investigate the presence of functional link between sleep and glucose metabolism, the influences of orexin antagonists with or without sleep-promoting effects were compared on glucose metabolism in diabetic mice. In db/db mice, 2-SORA-MK1064 (an orexin-2 receptor antagonist) and DORA-12 (a DORA) acutely improved non-rapid eye movement sleep, whereas 1-SORA-1 (an orexin-1 receptor antagonist) had no effect. Chronic resting-phase administration of these drugs improved glucose intolerance, without ...

Orexins are neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested. Mutations in orexin gene are a cause of narcolepsy 1 (NRCLP1) due to a deficient orexin system and low level of rexins in the brain and cerebrospinal fluid of narcoleptic patients. Orexin A binds to both orexin receptor type 1 and 2 (OX1R and OX2R) with a high affinity, whereas orexin B binds only to OX2R with a similar high affinity. Orexin B Peptide is 28 aa long corresponding to aa 70-97 of orexin precursor after cleavage into Orexin A and B.. ...

Orexins (also known as hypocretins), which are hypothalamic neuropeptides, play critical roles in the regulation of sleep/wakefulness states by activating two G-protein coupled receptors (GPCRs), orexin 1 (OX1R) and orexin 2 receptors (OX2R). In order to know the difference between effects of OX2R-selective antagonists (2-SORA) and dual orexin receptor antagonists (DORA), and to understand the mechanisms underlying orexin-mediated regulation of sleep/wakefulness states, we examined the effects of a newly developed 2-SORA, Compound 1m (C1m), and a DORA, suvorexant, on sleep/wakefulness states in C57BL/6J mice. After oral administration in the dark period, both C1m and suvorexant exhibited potent sleep-promoting properties with similar efficacy in a dose-dependent manner. While C1m did not increase NREM and REM sleep episode durations, suvorexant induced longer episode durations of NREM and REM sleep as compared with both the vehicle- and C1m-administered groups. When compounds were injected during light

Hypothalamic neuropeptide orexin has been implicated in the pathophysiology of psychiatric disorders and accumulating clinical evidence indicates a potential link between orexin and depression. However, the exact role of orexin in depression, particularly the underlying neural substrates and mechanisms, remains unknown. In this study, we reveal a direct projection from the hypothalamic orexinergic neurons to the ventral pallidum (VP), a structure that receives an increasing attention for its critical position in rewarding processing, stress responses, and depression. We find that orexin directly excites GABAergic VP neurons and prevents depressive-like behaviors in rats. Two orexin receptors, OX1R and OX2R, and their downstream Na+-Ca2+ exchanger and L-type Ca2+ channel co-mediate the effect of orexin. Furthermore, pharmacological blockade or genetic knockdown of orexin receptors in VP increases depressive-like behaviors in forced swim test and sucrose preference test. Intriguingly, blockage of

OX2R, orexin 2 receptor; OX2R; orexin A/orexin B receptor; orexin receptor, Ox2-R; Ox-2-R; hypocretin receptor type 2; Ox2-R; orexin receptor type ...

TABLE-US-00001 TABLE 1 Example compounds and characterization Example LC-MS IC50Ox1 IC50Ox2 No Chemical Name tR in min; [M + H].sup.+ [nM] [nM] 1 (S)-1-(5-Bromo-thiophene-2-sulfonyl)-pyrrolidine-2- 0.86; 461.1 20 .sup.*2 10 .sup.*2 carboxylic acid (3-methylsulfanyl-phenyl)-amide 2 (S)-1-(5-Bromo-thiophene-2-sulfonyl)-pyrrolidine-2- 0.92; 499.1 149 104 carboxylic acid (3-trifluoromethoxy-phenyl)-amide 3 (S)-1-(3-Methoxy-benzenesulfonyl)-pyrrolidine-2- 0.81; 407.2 28 8 carboxylic acid (3-methylsulfanyl-phenyl)-amide 4 (S)-1-(4-Propyl-benzenesulfonyl)-pyrrolidine-2- 0.92; 419.3 91 47 carboxylic acid (3-methylsulfanyl-phenyl)-amide 5 (S)-1-(4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7- 0.83; 447.6 128 27 sulfonyl)-pyrrolidine-2-carboxylic acid (3-methylsulfanyl- phenyl)-amide 6 (S)-1-(4-Methoxy-benzenesulfonyl)-pyrrolidine-2- 0.80; 407.3 21 .sup.*3 3 .sup.*3 carboxylic acid (3-methylsulfanyl-phenyl)-amide 7 (S)-1-(3-Chloro-benzenesulfonyl)-pyrrolidine-2- 0.85; 411.2 8 2 carboxylic acid ...

The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein selectively binds the hypothalamic neuropeptide orexin A. A related gene (HCRTR2) encodes a G-protein coupled receptor that binds orexin A and orexin B. [provided by RefSeq, Jan 2009 ...

Scientific background Lemberoxant (E2006) is a potent, brain-penetrant dual orexin 1/orexin 2 receptor antagonist. Lemberoxant binds to both orexin receptors and functionally inhibits them in a competitive manner with low nanomolar potency1.. Orexins are highly conserved proteins known to control feeding behavior, sleep-wake rhythm, reward and addiction and energy balance. In addition, several reports show that orexin/receptor pathways are involved in pathological processes of neurological diseases such as narcolepsy, depression, ischemic stroke, drug addiction and Alzheimers disease2.. ...

Orexin neuropeptides influence multiple homeostatic functions and play an essential role in the expression of normal sleep-wake behavior. While their two known receptors (OX1 and OX2) are targets for novel pharmacotherapeutics, the actions mediated by each receptor remain largely unexplored. Using brain slices from mice constitutively lacking either receptor, we used whole-cell and Ca2+ imaging methods to delineate the cellular actions of each receptor within cholinergic [laterodorsal tegmental nucleus (LDT)] and monoaminergic [dorsal raphe (DR) and locus coeruleus (LC)] brainstem nuclei-where orexins promote arousal and suppress REM sleep. In slices from OX−/−2 mice, orexin-A (300 nM) elicited wild-type responses in LDT, DR, and LC neurons consisting of a depolarizing current and augmented voltage-dependent Ca2+ transients. In slices from OX−/−1 mice, the depolarizing current was absent in LDT and LC neurons and was attenuated in DR neurons, although Ca2+-transients were still augmented. Since

The hypothalamus plays a central role in the integrated control of feeding and energy homeostasis. We have identified two novel neuropeptides, both derived from the same precursor by proteolytic processing, that bind and activate two closely related (previously) orphan G protein-coupled receptors. T …

Hypocretin (orexin) receptor 1; Ox1r; Ox-1-R; Ox1-R Orexin or hypocretin; a peptide that resembles the molecular structure of the gastric peptide secretin, was discovered in 1996 by two independent...

Abstract. Orexin/hypocretin neuropeptides, produced by a few thousand neurons in the lateral hypothalamus, are of critical importance for the control of vigilance and arousal of vertebrates, from fish to amphibians, birds and mammals. Two orexin peptides, called orexin-A and orexin-B, exist in mammals. They bind with different affinities to two distinct, widely distributed, excitatory G-protein- coupled receptors, orexin receptor type 1 and type 2 (OXR-1/2). The discovery of an OXR mutation causing canine narcolepsy, the narcolepsy-like phenotype of orexin peptide knockout mice, and the orexin neuron loss associated with human narcoleptic patients laid the foundation for the discovery of small molecule OXR antagonists as novel treatments for sleep disorders. Proof of concept studies from Glaxo Smith Kline, Actelion Pharmaceuticals Ltd. and Merck have now consistently demonstrated the efficacy of dual OXR antagonists (DORAs) in promoting sleep in rodents, dogs, non-human primates and humans. Some ...

Orexin B is a hypothalamatic neuropeptide stimulating food intake in rats. Orexin B activates OX2 receptors. Both OX1 and OX2 receptors are involved in maintaining arousal. OX2 receptors appear to be inhibitory autoreceptors on orexin-containing neurons. Orexin B stimulates food consumption i...

Orexin-A (hypocretin-1) and orexin-B (hypocretin-2) are hypothalamic neuropeptides that play key roles in the regulation of wakefulness, feeding, reward, autonomic functions and energy homeostasis. To control these functions indispensable for survival, orexin-expressing neurones integrate peripheral metabolic signals, interact with many types of neurones in the brain and modulate their activities via the activation of orexin-1 receptor or orexin-2 receptor. In addition, a new functional role of orexin is emerging in the regulation of insulin and leptin sensitivities responsible for whole-body glucose metabolism. Recent evidence indicates that orexin efficiently protects against the development of peripheral insulin resistance induced by ageing or high-fat feeding in mice. In particular, the orexin receptor-2 signalling appears to confer resistance to diet-induced obesity and insulin insensitivity by improving leptin sensitivity. In fact, the expression of orexin gene is known to be ...

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In 1998, reports of the discovery of orexin/hypocretin were published nearly simultaneously. Luis de Lecea, Thomas Kilduff, and colleagues reported the discovery of the hypocretin system at the same time as Takeshi Sakurai from Masashi Yanagisawas lab at the University of Texas Southwestern Medical Center at Dallas reported the discovery of the orexins to reflect the orexigenic (appetite-stimulating) activity of these peptides. In their 1998 paper describing these neuropeptides, they also reported discovery of two orexin receptors, dubbed OX1R and OX2R.[6] The two groups also took different approaches towards their discovery. One team was interested in finding new genes that were expressed in the hypothalamus. In 1996, scientists from the Scripps Research Institute reported the discovery of several genes in the rat brain, including one they dubbed clone 35. Their work showed that clone 35 expression was limited to the lateral hypothalamus.[9] They extracted selective DNA found in the lateral ...

The US Food and Drug Administration (FDA) today approved a first-in-class insomnia drug called suvorexant (Belsomra, Merck) after the manufacturer lowered the dosages to satisfy the agencys safety concerns. Merck announced that the FDA had declined to approve suvorexant until the starting dose for most patients was 10 mg. The agency also said that proposed upper-limit doses of 30 mg for elderly patients and 40 mg for nonelderly patients were unsafe. In a news release today, the FDA said it had approved suvorexant at 4 different strengths - 5 mg, 10 mg, 15 mg, and 20 mg. The total dosage in 1 day should not exceed 20 mg. Merck noted in its own news release today that the recommended dose is 10 mg for most patients, just as the FDA insisted. Suvorexant, an orexin receptor antagonist, is the first drug of its kind to be approved for patients with insomnia. It alters the signaling of orexins, neurotransmitters responsible for regulating the sleep-wake cycle. The FDA determined that suvorexant was ...

BACKGROUND:A specific group of neurons in the brain produces hypocretin, also called orexin, a peptide which has been established as an important regulator of anesthesia and emergence in the latest few years. In the animal experiment,we found that the level of orexin A in aged rats was higher when compared with that of the young ones. Whereas the numbers of both the orexin receptor 1 and 2 in aged rats decreased. We wonder if there is a similar phenomenon in human beings which might account for the difference between the intervals of elderly and young patients recovering from anesthesia. This study aims to investigate difference of plasma orexin A levels between elderly patients and young at emergence from sevoflurane-fentanyl anesthesia.. DESIGNING:Forty patients with ASA physical status I or II scheduled for elective lumbar surgery under general anesthesia (lasting for 2h to 4h)were enrolled. Anesthesia was induced with propofol 1-1.5mg/kg and fentanyl 2-3μg/kg. Following muscle relaxation ...

[Ala11,D-Leu15]-Orexin B(human) is a potent and selective orexin-2 receptor (OX2) agonist. [Ala11,D-Leu15]-Orexin B(human) shows a 400-fold selectivity for the OX2 (EC50=0.13 nM) over OX1 (52 nM). - Mechanism of Action & Protocol.

Recent studies have implicated the orexin system as a critical regulator of sleep/wake states as well as feeding behavior and reward processes. Orexin deficiency results in narcolepsy in humans, dogs, and rodents, suggesting that the orexin system is particularly important for maintenance of wakefulness. In addition, orexin deficiency also cause abnormalities in energy homeostasis and reward systems. Orexin activates waking active monoaminergic and cholinergic neurons in the hypothalamus and brainstem regions to maintain a long, consolidated waking period. Orexin neurons receive abundant input from the limbic system. Orexin neurons also have reciprocal links with the hypothalamic arcuate nucleus, which regulates feeding. Moreover, the responsiveness of orexin neurons to peripheral metabolic cues, such as leptin and glucose, suggest that these neurons have important role as a link between the energy homeostasis and vigilance states. Orexin neurons also have a link with the dopaminergic reward ...

Orexins A and B (ORA and ORB) are neuropeptide hormones found throughout the central nervous system and periphery. They are required for a host of physiological processes including mitogen-activated protein kinase (MAPK) regulation, steroidogenesis, appetite control and energy regulation. While some signalling mechanisms have been proposed for individual recombinant orexin receptors in generic mammalian cell types, it is clear that the peripheral effects of orexin are spatially and temporally complex. This study dissects the different G-protein signalling and MAPK pathways activated in a pluripotent human adrenal H295R cell line capable of all the physiological steps involved in steroidogenesis. Both extracellular receptor kinase 1/2 (ERK1/2) and p38 were phosphorylated rapidly with a subsequent decline, in a time- and dose-dependent manner, in response to both ORA and ORB. Conversely, there was little or no direct activation of the ERK5 or JNK pathway. Analysis using signalling and MAPK ...

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In addition, several studies in experimental animals have shown that eating at the wrong time of the sleep/wake cycle, i.e., during the sleep phase, favors the development of obesity.. In recent years it has become clear that the orexin system in the lateral hypothalamus is an important output pathway for the central biological clock, with pronounced effects on the sleep/wake-rhythm. Orexin is thought to be one of the main arousal systems in the brain, i.e., narcoleptic patients have a lack of orexin. CSF orexin levels show a pronounced day/night rhythm with peak levels being found during the active phase, both in nocturnal and diurnal species. In addition, as indicated by its name, orexin also stimulates appetite and our own experiments have shown that orexin stimulates hepatic glucose production via the autonomic nervous system.. The current project aims to test the hypothesis that a disturbed day/night rhythmicity of the hypothalamic orexin system is responsible for the deleterious effects of ...

Kukkonen JP; G-protein-dependency of orexin/hypocretin receptor signalling in recombinant Chinese hamster ovary cells.; Biochem Biophys Res Commun, 2016 PubMed Europe PMC ...

Kukkonen JP; G-protein-dependency of orexin/hypocretin receptor signalling in recombinant Chinese hamster ovary cells.; Biochem Biophys Res Commun, 2016 PubMed Europe PMC Scholia ...

Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurological disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O-GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs ...

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Complete information for HCRTR2 gene (Protein Coding), Hypocretin Receptor 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium

The hypothalamus integrates hormonal and neuronal signals to regulate appetite and energy metabolism and, thus, plays a crucial role in the homeostatic control of body weight. Additional neuronal circuits such as the dopaminergic and serotonergic systems of the brain can influence and eventually override this system. Recent studies suggest that orexinergic neurons in the lateral hypothalamus interact with both systems to integrate processes that regulate body weight, reward and sleep/wake states. The aim of this project is to define the role of orexin signalling in the cross-talk between homeostatic and hedonic circuits in control of energy homeostasis ...

Orexins or hypocretins are neurotransmitters produced by a small population of neurons in the lateral hypothalamus. This family of peptides modulates sleep‑wake cycle, arousal and feeding behaviors; however, the mechanisms regulating their expression remain to be fully elucidated. There is an interest in defining the key molecular elements in orexin regulation, as these may serve to identify targets for generating novel therapies for sleep disorders, obesity and addiction. Our previous studies showed that the expression of orexin was decreased in mice carrying null‑mutations of the transcription factor early B‑cell factor 2 (ebf2) and that the promoter region of the prepro‑orexin (Hcrt) gene contained two putative ebf‑binding sites, termed olf‑1 sites ...

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The hypocretin system influences various brain functions by modulation of synaptic transmission. Electrophysiological data show that Hcrt can act both

Anti-Orexin Receptor 2 Antibody from Alomone Labs is a highly specific rabbit polyclonal Ab directed against an epitope of rat OX2R. Applications: ICC, IHC, WB. Free samples available. Control antigen included. Lyophilized. Global shipping at room temperature. Your top supplier for Hypocretin receptor research!

Rabbit polyclonal antibody raised against synthetic peptide of HCRTR1. A synthetic peptide corresponding to 14 amino acids from 2nd extracellular domain of human HCRTR1. (PAB26602) - Products - Abnova

Scientists at the University of Texas have uncovered a new hormonal cascade that is concerned with the regulation of feeding behaviour. The discovery may eventually lead to new drug treatment for obesity, diabetes, and cachexia.. The researchers identified centrally acting neuropeptides and their associated receptors, which they named orexin A and B and OX-1R and OX-2R respectively (Cell 1998; 92:573-83). The orexins are produced in the lateral hypothalamus, an area of the brain known to be concerned with the sensation … ...

* Findings suggest drug may not impair memory, attention * Mercks sleep drug now before FDA By Julie...

TY - JOUR. T1 - Both orexin 1 and 2 receptors mediate orexin a induced sympathoexcitaton and increase in phrenic nerve activity. AU - Shahid, Israt Z.. AU - Rahman, Ahmed A.. AU - Pilowsky, Paul M.. PY - 2011. Y1 - 2011. N2 - Orexin containing neurons in the lateral hypothalamus project to all levels of the spinal cord including dorsal horn, intermediolateral cell column and ventral horn. This study was undertaken to determine the role of orexin receptors in the spinal cord. Experiments were conducted on anesthetized, vagotomised and artificially ventilated Sprague-Dawley rats (n = 17). Intrathecal injection of orexin A (OX-A) (20 nmol) caused increase in mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic nerve activity (sSNA) and phrenic nerve activity (PNA). But orexin receptor 1 antagonist, SB 334867 (200 nmol), was unable to affect the resting level of cardio-respiratory parameters when injected intrathecally. On the other hand SB 334867, injected 20 min before OX-A (20 ...

The researchers designed a series of experiments in rats to study the role of orexins in the anesthesia-arousal cycle. They focused on the effects of propofol-a drug widely used not only for anesthesia but also as a sedative.. The orexins are a relatively recently discovered group of peptides expressed by neurons (nerve cells) in specific areas of the brain. Accumulated evidence suggests that orexinergic [orexin-producing] neurons play a critical role in the promotion and the maintenance of wakefulness, the researchers write.. In the experiments, when rats were placed under propofol anesthesia, the activity of orexinergic neurons dropped sharply. When the rats emerged from anesthesia, orexinergic neuron activity returned to normal. Levels of orexin-A in the blood also decreased during propofol anesthesia. As in previous studies, the orexin-producing neurons were localized to a region called the basal forebrain.. In further experiments, anesthetized rats underwent injection of micro-level ...

The researchers designed a series of experiments in rats to study the role of orexins in the anesthesia-arousal cycle. They focused on the effects of propofol-a drug widely used not only for anesthesia but also as a sedative.. The orexins are a relatively recently discovered group of peptides expressed by neurons (nerve cells) in specific areas of the brain. Accumulated evidence suggests that orexinergic [orexin-producing] neurons play a critical role in the promotion and the maintenance of wakefulness, the researchers write.. In the experiments, when rats were placed under propofol anesthesia, the activity of orexinergic neurons dropped sharply. When the rats emerged from anesthesia, orexinergic neuron activity returned to normal. Levels of orexin-A in the blood also decreased during propofol anesthesia. As in previous studies, the orexin-producing neurons were localized to a region called the basal forebrain.. In further experiments, anesthetized rats underwent injection of micro-level ...

Orexin signaling is essential for normal regulation of arousal and behavioral state control and represents an attractive target for therapeutics combating insomnia. Alternatively termed hypocretins, these neuropeptides were named to reflect sequence similarity to incretins and their potential to promote feeding. Current nomenclature reflects these molecular and biochemical discovery approaches in which HCRT, HCRTR1, and HCRTR2 genes encode prepro-orexin, the orexin 1 receptor (OX1) and the orexin 2 receptor (OX2)-gene names designated by the Human Genome Organization and receptor names designated by the International Union of Basic and Clinical Pharmacology. Orexinergic neurons are most active during wakefulness and fall silent during inactive periods, a prolonged disruption in signaling most profoundly resulting in hypersomnia and narcolepsy. Hcrtr2 mutations underlie the etiology of canine narcolepsy, deficiencies in orexin-producing neurons are observed in the human disorder, and ablation of ...

We used Fos immunohistochemistry to investigate the relation between orexin neuron activity, behavioral state,Tb, and LMA. We found that Fos expression in perifornical orexin neurons was common after periods of wakefulness but uncommon after periods of NREM and REM sleep. Orexin neuron Fos expression exhibited a circadian pattern under both LD and DD conditions; in experiments 1 and 3, this Fos expression also correlated with Tb and LMA.. Several methodological issues warrant discussion. First, Fos is a useful marker of activity in neurochemically defined neurons, often indicating an increase in synaptic activity or a rise in the intracellular concentrations of cAMP or calcium (for review, seeCirelli and Tononi, 2000). Still, Fos immunohistochemistry has some limitations. Fos protein may persist in neurons for several hours after a stimulus (Schwartz et al., 1994), and its presence may reflect the summation of neuronal activity over time. Thus, the correlation of orexin neuron activity with ...

To assess the role of orexin receptor signaling in neuron-like cells, Neuro-2a murine neuroblastoma and PC12 human pheochromocytoma cells were stably transfected with human OX(1) or OX(2) receptors. Activation of both receptors strongly elevated cellular inositol phosphates and Ca(2+). A difference …

Glucoprivation activates neurons in the perifornical hypothalamus (PeH) and in the rostral ventrolateral medulla (RVLM), which results in release of adrenaline. The current study aimed to establish (i) whether neuroglucoprivation in the PeH or in the RVLM elicits adrenaline release in vivo; and (ii) whether direct activation by glucoprivation or orexin release in the RVLM modulates the adrenaline release. Neuroglucoprivation in the PeH or RVLM was elicited by microinjections of 2-deoxy-D-glucose or 5-thio-D-glucose in anesthetized, euglycemic, rats. We found that inhibition of neurons in the PeH abolished the increase in adrenal sympathetic nerve activity (ASNA) to systemic glucoprivation. Secondly, glucoprivation of neurons in the PeH increased ASNA. Thirdly, in vivo or in vitro glucoprivation did not affect the activity of RVLM adrenal premotor neurons. Finally, blockade of orexin receptors in the RVLM abolished the increase in ASNA to neuroglucoprivation in the PeH. The evoked changes in ASNA ...

Introduction: Previous studies have investigated the effects and importance of orexin and estradiol on food intake. In this study the effects of orexin on estradiol release by the ventromedial hypothalamus (satiety center) and lateral hypothalamus (feeding center) have been investi-gated. Forty adult male rats, divided to two groups, the control ...

An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients. Neurobiol Dis. 2008 Apr; 30(1):74-83 ...

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The IUPHAR/BPS Guide to Pharmacology. [3H]-almorexant ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.

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Suvorexant - Get up-to-date information on Suvorexant side effects, uses, dosage, overdose, pregnancy, alcohol and more. Learn more about Suvorexant

According to a Stanford University study, infections of the upper airway like the H1N1 virus responsible for the swine flu pandemic may trigger the onset of the sleep disorder narcolepsy.

One vaccine used in Europe during the 2009 swine flu pandemic was linked to rare cases of a baffling side effect -- the sleep disorder narcolepsy. Now new research offers a clue to what happened.

The perifornical lateral hypothalamic area (PeFLH), which houses orexin/hypocretin (OX) neurons, is thought to play an important role in arousal, feeding, and locomotor activity. The present study examined behavioural ...

Baranowska B, Wolińska-Witort E, Martyńska L, Martyńska M, Chmielowska M, Baranowska-Bik A. Plasma orexin A, orexin B, leptin, neuropeptide Y (NPY) and insulin in obese women. Neuro Endocrinol Lett. 2005 Aug; 26(4): 293-296 ...

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