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Orexin B (human)

Endogenous agonist at OX1 and OX2 CAS# 205640-91-1

Orexin B (human)

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Chemical structure

Orexin B (human)

3D structure

Chemical Properties of Orexin B (human)

Cas No. 205640-91-1 SDF Download SDF
PubChem ID 90479794 Appearance Powder
Formula C123H212N44O35S M.Wt 2899.36
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 1 mg/ml in water
Sequence RSGPPGLQGRLQRLLQASGNHAAGILTM

(Modifications: Met-28 = C-terminal amide)

SMILES CCC(C)C(C(=O)NC(CC(C)C)C(=O)NC(C(C)O)C(=O)NC(CCSC)C(=O)N)NC(=O)CNC(=O)C(C)NC(=O)C(C)NC(=O)C(CC1=CNC=N1)NC(=O)C(CC(=O)N)NC(=O)CNC(=O)C(CO)NC(=O)C(C)NC(=O)C(CCC(=O)N)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C(CCC(=O)N)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)CNC(=O)C(CCC(=O)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C2CCCN2C(=O)C3CCCN3C(=O)CNC(=O)C(CO)NC(=O)C(CCCNC(=N)N)N
Standard InChIKey DHBREICAXZPFDD-WMQZXSDYSA-N
Standard InChI InChI=1S/C123H212N44O35S/c1-18-63(12)96(118(200)161-80(46-62(10)11)116(198)165-97(67(16)170)119(201)152-70(98(129)180)35-41-203-17)164-94(178)53-140-99(181)64(13)146-100(182)65(14)148-110(192)81(47-68-49-136-57-145-68)160-115(197)82(48-90(128)174)151-92(176)51-142-104(186)83(55-168)162-101(183)66(15)147-106(188)74(30-33-88(126)172)155-113(195)78(44-60(6)7)159-114(196)79(45-61(8)9)158-108(190)72(26-21-38-139-123(134)135)153-109(191)75(31-34-89(127)173)156-112(194)77(43-59(4)5)157-107(189)71(25-20-37-138-122(132)133)149-91(175)50-141-103(185)73(29-32-87(125)171)154-111(193)76(42-58(2)3)150-93(177)52-143-117(199)85-27-22-40-167(85)120(202)86-28-23-39-166(86)95(179)54-144-105(187)84(56-169)163-102(184)69(124)24-19-36-137-121(130)131/h49,57-67,69-86,96-97,168-170H,18-48,50-56,124H2,1-17H3,(H2,125,171)(H2,126,172)(H2,127,173)(H2,128,174)(H2,129,180)(H,136,145)(H,140,181)(H,141,185)(H,142,186)(H,143,199)(H,144,187)(H,146,182)(H,147,188)(H,148,192)(H,149,175)(H,150,177)(H,151,176)(H,152,201)(H,153,191)(H,154,193)(H,155,195)(H,156,194)(H,157,189)(H,158,190)(H,159,196)(H,160,197)(H,161,200)(H,162,183)(H,163,184)(H,164,178)(H,165,198)(H4,130,131,137)(H4,132,133,138)(H4,134,135,139)/t63-,64-,65-,66-,67+,69-,70-,71-,72-,73-,74-,75-,76-,77-,78-,79-,80-,81-,82-,83-,84-,85-,86-,96-,97-/m0/s1
General tips For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.
We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months.
Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it.
About Packaging 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial.
2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial.
3. Try to avoid loss or contamination during the experiment.
Shipping Condition Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request.

Biological Activity of Orexin B (human)

DescriptionEndogenous agonist at orexin receptors (Ki values are 420 and 36 nM for OX1 and OX2 receptors, respectively). Stimulates feeding following central administration and may be involved in the control of sleep-wake cycle and other hypothalamic functions. Also neuroprotective for dopaminergic neurons in rat midbrain cultures.

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References on Orexin B (human)

Human pheochromocytomas express orexin receptor type 2 gene and display an in vitro secretory response to orexins A and B.[Pubmed:11600547]

J Clin Endocrinol Metab. 2001 Oct;86(10):4818-21.

Orexins A and B are hypothalamic peptides, that act through two receptor subtypes, called OX1-R and OX2-R. OX1-R selectively binds orexin A, whereas OX2-R is nonselective for both orexins. High levels of OX1-R mRNA and low levels of OX2-R mRNA have been previously detected in the human adrenal cortex and medulla. Here we demonstrated by RT-PCR the expression of the OX2-R, but not the OX1-R, gene in 10 benign secreting pheochromocytomas. Both orexins A and B stimulated catecholamine secretion from pheochromocytoma slices; the maximal effective concentration was 10(-8) mol/liter. Orexins A and B (10(-8) mol/liter) increased IP3, but not cAMP production, by tumor slices, and the effect was blocked by the PLC inhibitor U-73122. The catecholamine response to 10(-8) mol/liter orexins A and B was abolished by either U-73122 or the PKC antagonist calphostin C and was unaffected by the adenylate cyclase inhibitor SQ-22536 and the PKA inhibitor H-89. Collectively, these findings suggest that orexins stimulate catecholamine secretion from human pheochromocytomas, acting through OX2-R coupled to the PLC-PKC signaling pathway.

Orexin receptor expression in human adipose tissue: effects of orexin-A and orexin-B.[Pubmed:17065396]

J Endocrinol. 2006 Oct;191(1):129-36.

Orexin-A and orexin-B, via their receptors orexin-1 receptor (OX1R) and orexin-2 receptor (OX2R) have been shown to play a role in the regulation of feeding, body weight, and energy expenditure. Adipose tissue also contributes significantly to the maintenance of body weight by interacting with a complex array of bioactive peptides; however, there are no data as yet on the expression of orexin components in adipose tissue. We, therefore, analyzed the expression of OX1R and OX2R in human adipose tissue and determined functional responses to orexin-A and orexin-B. OX1R and OX2R mRNA expression was detected in subcutaneous (s.c.) and omental adipose tissue and in isolated adipocytes. Protein for OX1R and OX2R was also detected in whole adipose tissue sections and lysates. Treatment with orexin-A, and orexin-B (100 nM, 24 h) resulted in a significant increase in peroxisome proliferator-activated receptors gamma-2 mRNA expression in s.c. adipose tissue (P < 0.05). Hormone sensitive lipase mRNA was significantly reduced in omental adipose tissue with orexin-A and orexin-B treatment (P < 0.05). Glycerol release from omental adipose tissue was also significantly reduced with orexin-A treatment (P < 0.05). These findings demonstrate for the first time the presence of functional orexin receptors in human adipose tissue and suggest a role for orexins in adipose tissue metabolism and adipogenesis.

Structure-activity studies of orexin a and orexin B at the human orexin 1 and orexin 2 receptors led to orexin 2 receptor selective and orexin 1 receptor preferring ligands.[Pubmed:14971895]

J Med Chem. 2004 Feb 26;47(5):1153-60.

The neuropeptides orexin A and B (also known as hypocretins) play an important role in many physiological and behavioral activities. Orexins are ligands of two closely related G-protein-coupled receptors, that are the named orexin 1 and orexin 2 receptors. To clearly identify the minimal ligand sequences required for receptor activation, we synthesized and analyzed different centrally, C- and N-terminally truncated analogues of orexins A and B. Furthermore, we used the shortest active analogue to screen for important amino acid residues by l-alanine and l-proline replacement scans. For orexin A, only full-length peptides were able to show the same activity as orexin A, but interestingly, reduced orexin A and natural orexin A, which contains the two disulfide bonds, had the same activity. The shortest highly active orexin B analogue was orexin B 6-28. In addition, we identified orexin A 2-33 as the first analogue with orexin 1 receptor preference and orexin B 10-28, [A27]orexin B 6-28, and [P11]orexin B 6-28 as being highly potent orexin 2 receptor selective (>1000-fold) peptides.

Orexin-stimulated MAP kinase cascades are activated through multiple G-protein signalling pathways in human H295R adrenocortical cells: diverse roles for orexins A and B.[Pubmed:19460850]

J Endocrinol. 2009 Aug;202(2):249-61.

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 inhibitors as well as receptor-specific antagonists determined the precise mediators of the orexin response in these cells. Both ERK1/2 and p38 activation were predominantly G(q)- and to a lesser extent G(s)-mediated; p38 activation even had a small G(i)-component. Effects were broadly comparable for both orexin sub-types ORA and ORB and although most of the effects were transmitted through the orexin receptor-1 subtype, we did observe a role for orexin receptor-2-mediated activation of both ERK1/2 and p38. Cortisol secretion also differed in response to ORA and ORB. These data suggest multiple roles for orexin-mediated MAPK activation in an adrenal cell-line, this complexity may help to explain the diverse biological actions of orexins with wide-ranging consequences for our understanding of the mechanisms initiated by these steroidogenic molecules.

The hypocretin/orexin ligand-receptor system: implications for sleep and sleep disorders.[Pubmed:10906799]

Trends Neurosci. 2000 Aug;23(8):359-65.

The molecules originally described as the hypocretins and subsequently as the orexins were initially implicated in the control of food intake. Recent observations implicate this newly-described neurotransmitter system in the sleep disorder narcolepsy and, potentially, in the regulation of normal sleep processes. This article reviews the research that led to the isolation of the hypocretin/orexin peptides, their receptors and the activity of these molecules as we currently understand them. A model is proposed in which the cells that make these peptides might be involved in arousal state control.

Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior.[Pubmed:9491897]

Cell. 1998 Feb 20;92(4):573-85.

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. These peptides, termed orexin-A and -B, have no significant structural similarities to known families of regulatory peptides. prepro-orexin mRNA and immunoreactive orexin-A are localized in neurons within and around the lateral and posterior hypothalamus in the adult rat brain. When administered centrally to rats, these peptides stimulate food consumption. prepro-orexin mRNA level is up-regulated upon fasting, suggesting a physiological role for the peptides as mediators in the central feedback mechanism that regulates feeding behavior.

Description

Orexin B, human is an endogenous agonist at Orexin receptor with Kis of 420 and 36 nM for OX1 and OX2, respectively.

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