Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
11-SEPTEMBER-2008 12:20:15 - Orexin Solution phase NMR structure of orexin A based on the PDB coordinates 1R02. Prepro-orexin Identifiers Symbol Orexin Pfam PF02072 InterPro IPR001704 SCOP 1cq0 OPM family 154 OPM protein 1wso Available PDB structures: 1cq0A:71-97 1wsoA:35-66 1r02A:34-66 1uvqC:1-13 Solution phase NMR structure of orexin B based on the PDB coordinates 1CQ0. hypocretin orexin neuropeptide precursor Identifiers Symbol HCRT Alt. Symbols PPOX, OX Entrez 3060 HUGO 4847 OMIM 602358 RefSeq NM_001524 UniProt O43612 Other data Locus Chr. 17 q21 Orexins, also called hypocretins, are the common names given to a pair of highly excitatory neuropeptide hormones that were simultaneously discovered by two groups of researchers in rat brains.12 The two related peptides Orexin-A and B, or hypocretin-1 and -2, with approximately 50% sequence identity, are produced by cleavage of a single precursor protein. Orexin-A/hypocretin-1 is consisted of 33 aminoacid residues and has two intrachain disulfide bonds, while Orexin-B/hypocretin-2 is a linear 28 aminoacid residue peptide. Studies suggest that orexin A/hypocretin-1 may be of greater biological importance than orexin B/hypocretin-2. Although these peptides are produced by a very small population of cells in the lateral and posterior hypothalamus, they send projections throughout the brain. The orexin peptides bind to the orexin receptor, a G-protein coupled receptor. The orexins/hypocretins are strongly conserved peptides, found in all major classes of vertebrates. The peptides are thought to have arisen early in vertebrate evolution. Contents 1 Functions 1.1 Wakefulness 1.2 Food intake 1.3 Pharmacologic potential 2 History and nomenclature 3 Drugs 4 See also 5 References 6 External links Functions The orexin/hypocretin system was initially suggested to be primarily involved in the stimulation of food intake, based on the finding that central administration of orexin A/hypocretin-1 increases food intake. In addition, it stimulates wakefulness and energy expenditure. Wakefulness Orexin seems to promote wakefulness. The discovery that orexin/hypocretin dysregulation causes the sleep disorder narcolepsy3 in mice subsequently indicated a major role for this system in sleep regulation. Narcolepsy results in excessive daytime sleepiness, inability to consolidate wakefulness in the day and sleep at night, and cataplexy loss of muscle tone in response to strong, usually positive, emotions. Dogs that lack a functional receptor for orexin/hypocretin have narcolepsy, while animals and people lacking the orexin/hypocretin neuropeptide itself also have narcolepsy. Orexin/hypocretin neurons strongly excite various brain nuclei with important roles in wakefulness including the dopamine, norepinephrine, histamine and acetylcholine systems and appear to play an important role in stabilizing wakefulness and sleep. Recent studies indicate that a major role of the orexin/hypocretin system is to integrate metabolic, circadian and sleep debt influences to determine whether the animal should be asleep or awake and active. Central administration of orexin A/hypocretin-1 strongly promotes wakefulness, increases body temperature, locomotion and elicits a strong increase in energy expenditure. Sleep deprivation also increases orexin A/hypocretin-1 transmission. The orexin/hypocretin system may thus be more important in the regulation of energy expenditure than food intake. In fact, orexin/hypocretin-deficient narcoleptic patients have increased obesity rather than decreased BMI, as would be expected if orexin/hypocretin were primarily an appetite stimulating peptide. Another indication that deficits of orexin cause narcolepsy is that depriving monkeys of sleep for 30-36 hours and then injecting them with the neurochemical alleviates the cognitive deficiencies normally seen with such amount of sleep loss.45 Recently, transgenic mice have been engineered to lack the gene for orexin. Transitioning frequently and rapidly between sleep and wakefulness, these mice display many of the symptoms of narcolepsy. Researchers are using this animal model of narcolepsy to study the disease.6 Food intake Orexin increases the craving for food, and correlates with the function of the substances that promote its production. Leptin is a hormone produced by fat cells and acts as a long-term internal measure of energy state. Ghrelin is a short-term factor secreted by the stomach just before an expected meal, and strongly promotes food intake. Hypocretin-producing cells have recently been shown to be inhibited by leptin by leptin receptors, but are activated by ghrelin and hypoglycemia glucose inhibits orexin production. Orexin/hypocretin, as of 2007, is claimed to be a very important link between metabolism and sleep regulation. Such a relationship has been long suspected, based on the observation that long-term sleep deprivation in rodents dramatically increases food intake and energy metabolism, i.e., catabolism, with lethal consequences on a long-term basis. Pharmacologic potential The research on orexin/hypocretin is still in an early phase, although many scientists believe that orexin/hypocretin-based drugs could help narcoleptics and increase alertness in the brain without the side effects of amphetamines. Preliminary research has been conducted that shows potential for orexin blockers in the treatment of alcoholism. Lab rats given drugs which targeted the orexin system lost interest in alcohol despite being given free access in experiments.78 Finally, a recent study reported that transplantation of orexin/hypocretin neurons into the pontine reticular formation in rats is feasible, indicating the development of alternative therapeutic strategies in addition to pharmacological interventions to treat narcolepsy.9 History and nomenclature Masashi Yanagisawa and colleagues at the University of Texas Southwestern Medical Center at Dallas, coined the term orexin to reflect the orexigenic appetite-stimulating activity of these hormones. 1 Luis DeLecea, Thomas Kilduff, and colleagues also reported discovery of these same peptides, dubbing them hypocretins to indicate that they are synthesized in the hypothalamus and to reflect their similarity to a class of hormones called incretins i.e., hypothalamic incretin.2 The name of this family of peptides is currently in dispute. The name orexin has been rejected by some due to evidence that the orexigenic effects of these peptides may be incidental or trivial i.e., hypocretin induced subjects eat more because they are awake more, while other groups maintain that the name hypocretin is awkward, pointing out that many neuropeptides have names that are unrelated to their most important functions, and that waking is one of the important factors that supports feeding behavior. The name hyporexin has been suggested as a compromise, but as of yet has not been commonly used. Both orexin and hypocretin will likely continue to appear in published works until a preferred name has been accepted by the scientific community. Drugs SB649868 is under development by GlaxoSmithKline for sleep disorders; it is an orexin receptor antagonist. ACT-078573 is a similar compound under development by Actelion. See also Leptin References ^ a b Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M 1998. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92 4: 573-85. doi:10.1016/S0092-86740080949-6. PMID 9491897. ^ a b de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel WN, van den Pol AN, Bloom FE, Gautvik KM, Sutcliffe JG 1998. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc. Natl. Acad. Sci. U.S.A. 95 1: 322-7. doi:10.1073/pnas.95.1.322. PMID 9419374. ^ Siegel JM 1999. Narcolepsy: a key role for hypocretins orexins. Cell 98 4: 409-12. doi:10.1016/S0092-86740081969-8. PMID 10481905. ^ Alexis Madriga 2007-12-28. Snorting a Brain Chemical Could Replace Sleep. Wired News, Condé Nast. Retrieved on 2008-02-05. ^ Deadwyler SA, Porrino L, Siegel JM, Hampson RE 2007. Systemic and nasal delivery of orexin-A Hypocretin-1 reduces the effects of sleep deprivation on cognitive performance in nonhuman primates. J. Neurosci. 27 52: 14239-47. doi:10.1523/JNEUROSCI.3878-07.2007. PMID 18160631. ^ Mochizuki T, Crocker A, McCormack S, Yanagisawa M, Sakurai T, Scammell TE July 2004. Behavioral state instability in orexin knock-out mice. J. Neurosci. 24 28: 6291-300. doi:10.1523/JNEUROSCI.0586-04.2004. PMID 15254084. ^ Helen Puttick 2006-12-26. Hope in fight against alcoholism, The Herald. ^ Lawrence AJ, Cowen MS, Yang HJ, Chen F, Oldfield B 2006. The orexin system regulates alcohol-seeking in rats. Br. J. Pharmacol. 148 6: 752-9. doi:10.1038/sj.bjp.0706789. PMID 16751790. ^ Arias-Carrión O, Murillo-Rodriguez E, Xu M, Blanco-Centurion C, Drucker-Colín R, Shiromani PJ 2004. Transplantation of hypocretin neurons into the pontine reticular formation: preliminary results. Sleep 27 8: 1465-70. PMID 15683135. External links CIMIT Center for Integration of Medicine and Innovative Technology MeSH orexins v d e Peptides: neuropeptides Hypothalamic Somatostatin - CRH - GnRH - GHRH - Orexins - TRH - POMC ACTH, MSH, Lipotropin Gastrointestinal hormones Cholecystokinin - Gastric inhibitory polypeptide - Gastrin - Motilin - Secretin - Vasoactive intestinal peptide Other hormones Vasopressin - Calcitonin - Other Angiotensin - Bombesin/Neuromedin B - Calcitonin gene-related peptide - Carnosine - Delta sleep-inducing peptide - FMRFamide - Galanin - Gastrin releasing peptide - Kinins Bradykinin, Tachykinins - Neuromedin B, N, U - Neuropeptide Y - Neurophysins - Neurotensin - Opioid peptide - Pancreatic polypeptide - Pituitary adenylate cyclase activating peptide Retrieved from http://en..org/wiki/Orexin Categories: Genes on chromosome 17 | Endocrinology | Peptide hormones | Neuropeptides Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Dansk Deutsch Français Nederlands 日本語 Polski Suomi Svenska 中文 This page was last modified on 1 September 2008, at 18:50
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie Video
The Power of You Video
Effects of MonaVie Active on Antioxidant Capacity in Humans
Log into your Wholesale MonaVie Account
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.