Orexin A (bovine, human, mouse, rat)
Structure Gene, mRNA, and precursor Pathophysiological implications Synthesis and release Receptors Agonists and Antagonists Biological functions- Product Name
- Orexin A (bovine, human, mouse, rat)
- CAS No.
- 205640-90-0
- Chemical Name
- Orexin A (bovine, human, mouse, rat)
- Synonyms
- OREXIN A;HYPOCRETIN;Rat orexin A;Hypocretin 1;OREXIN A (HUMAN, RAT, MOUSE);Orexin A (human, mouse, rat);Rabbit Anti-Orexin A antibody;M.W. 3561.12 C152H243N47O44S4;OREXINS OREXIN A HUMAN, RAT, MOUSE;OREXIN A, BOVINE, HUMAN, MOUSE, RAT
- CBNumber
- CB9355020
- Molecular Formula
- C152H243N47O44S4
- Formula Weight
- 3561.1
- MOL File
- 205640-90-0.mol
Orexin A (bovine, human, mouse, rat) Property
- Density
- 1.53±0.1 g/cm3(Predicted)
- storage temp.
- -15°C
- solubility
- Soluble to 1 mg/ml in sterile
- form
- crystalline solid
- color
- White to off-white
- Water Solubility
- Soluble in water at 1mg/ml
- Sequence
- Glp-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-IIE-Leu-Thr-Leu-NH2 (Disulfide bridge: Cys6-Cys12, Cys7-Cys14)
Safety
- WGK Germany
- 3
- HS Code
- 2937190000
N-Bromosuccinimide Price
- Product number
- J65378
- Product name
- Orexin A, human, bovine, rat, mouse
- Packaging
- 0.5mg
- Price
- $450
- Updated
- 2021/12/16
- Product number
- 15073
- Product name
- Orexin A (bovine, human, mouse, rat)
- Purity
- ≥95%
- Packaging
- 500μg
- Price
- $287
- Updated
- 2024/03/01
- Product number
- 15073
- Product name
- Orexin A (bovine, human, mouse, rat)
- Purity
- ≥95%
- Packaging
- 1mg
- Price
- $486
- Updated
- 2024/03/01
- Product number
- 15073
- Product name
- Orexin A (bovine, human, mouse, rat)
- Purity
- ≥95%
- Packaging
- 5mg
- Price
- $2280
- Updated
- 2024/03/01
- Product number
- 1455
- Product name
- Orexin A human, rat, mouse
- Packaging
- 500U
- Price
- $535
- Updated
- 2021/12/16
Orexin A (bovine, human, mouse, rat) Chemical Properties,Usage,Production
Structure
Orexin exists as two molecular forms, orexin-A and
orexin-B, derived from the same 130-aa residue precursor
(prepro-orexin). In mammals, orexin-A is a 33 aa residue
peptide with an N-terminal glutamine cyclized to pyroglutamate, and two intrachain disulfide bonds that are
fully conserved among tetrapods. Orexin-B is a linear
28 aa residue peptide. Orexin-B consists of two α-helices
connected with a short linker. The C-termini of both orexins are amidated. Human orexin-A and orexin-B have
46% homology (13/28), with their C-terminal side in particular being conserved.
Although it was thought originally that orexin has no
functional or structural identity with any other known
regulatory peptide, it is now considered to belong to
the incretin gene family of peptides, including members
of the secretin-glucagon superfamily such as growth
hormone-releasing hormone, pituitary adenylate
cyclase-activating polypeptide, vasoactive intestinal peptide, and glucagon-like peptides. The molecular structures of orexins are relatively well conserved among
vertebrates, especially in the disulfide bond regions in
orexin-A and the C-terminal side in both orexins. Although tetrapod orexin-A comprises 33 aa residues, orexin-A of goldfish and zebrafish is 14 aa residues
longer due to an additional spacer sequence.
Gene, mRNA, and precursor
The human prepro-orexin gene (HCRT), located on
chromosome 17 (17q21), consists of two exons and one
intron. Orexin-A and -B are coded tandemly
in the prepro-orexin mRNA. To date, orexin has been
identified in vertebrates, but orexin-like sequences have
not been identified in invertebrates.
Pathophysiological implications
The dual orexin receptor antagonist suvorexant has been approved by the US Food and Drug Administration (FDA) for insomnia. Dual orexin receptor agonists such as almorexant, lemborexant, filorexant, and SB-649868 have been proceeded clinical trial. Suvorexant and other dual orexin receptor antagonists are being explored in a number of other indications, including depression, anxiety disorders, pain conditions, and degenerative disorders such as Alzheimer’s disease.
Synthesis and release
Orexin-A and orexin-B are synthesized in neurons located in the lateral hypothalamus. Food restriction increases orexin mRNA and peptide content in the brain. In cultured hypothalamic orexin neurons, low glucose concentration in the medium triggers the synthesis of orexins.
Receptors
There are two types of orexin receptors: orexin receptor-1 and -2 (OX1R and OX2R). The orexin receptors are GPCRs with seven-transmembrane domains. The amino acid sequence homology of human orexin receptors is mutually 64%. Orexin-A binds to OX1R and OX2R with a high affinity, whereas orexin-B selectively binds to OX2R with a similar high affinity. The human OX1R gene is located on chromosome 1 (1p35), and the human OX2R gene is located on chromosome 6 (6q11). OX1R and OX2R activate Gq pathways to produce IP3 and an intracellular rise in Ca2+, or to stimulate the MAPK pathway. Furthermore, OX2R is able to modulate the intracellular concentration of cAMP by coupling to Gs and Gi proteins.
Agonists and Antagonists
[Ala11, D-Leu15]-Orexin B and SB-668875 are OX2 specific agonists. Among orexin receptor antagonists, ACT-335827, SB-334867, and SB-408124 are OX1-specific antagonists; TCS-OX2-29, EMPA, and JNJ 10397049 are OX2-specific antagonists; and ACT-078573 (almorexant), MK-4305 (suvorexant), MK-6096 (filorexant), E-2006 (lemborexant), SB-649868, and TCS 1102 are dual antagonists. Further information regarding orexin receptor antagonists can be found in the review by Lebold and colleagues.
Biological functions
Although orexin was first reported as an appetite-stimulating hormone in mammals, further studies have revealed its multifunctional status. An important function of orexin is as a regulator of the sleep-wake cycle. Orexin affects monoaminergic neurons in the locus ceruleus, raphe nucleus, and ventral tegmental area to maintain wakefulness. Orexin systems have roles in regulating drinking behavior, locomotor activity, and sympathetic nervous system activation. Orexin contributes to the regulation of the endocrine system, elevating blood corticosterone levels, decreasing blood prolactin levels, and suppressing the gonadotropin-producing cells in the hypothalamus. In teleosts, the intracerebroventricular injection of orexin-A stimulates food consumption and locomotor activity in goldfish and zebrafish.
Uses
appetite regulation, wakefulness, locomotor activity, hypothalamic-pituitary-adrenal activity, and pain thresholds. Orexin signaling is activated by nutrient depletion, causing an increase in food intake by delaying the signals of satiety. It activates the orexin-1 and -2 receptors with equal affinity.
General Description
Orexin is a hypothalamic neuropeptide consisting of 33 or 28 aa residues. Orexin has a pleiotropic function regulating feeding behavior, the sleep-wake cycle, metabolism, locomotor activity, and the endocrine system through orexin receptors. Orexin (also known as hypocretin) was discovered by reverse pharmacology as an endogenous ligand for two orphan GPCRs in 1998.
Biological Activity
orexin a, a 33 amino acid hypothalamic neuropeptide, is an endogenous agonist at orexin-1 and -2 receptors[1]. it play a role in appetite regulation, wakefulness, locomotor activity, hypothalamic-pituitary-adrenal activity, and pain thresholds[2].orexin a (10 and 30 mg/kg i.v., 5 min pre-plantar test) increases the latency to thermally stimulated paw contraction to baseline levels. orexin a (3-30 mg/kg; i.v.; 5 min pre-test) significantly increases the reaction latency of intravenous reactions of 10 and 30 mg/kg[3].[1]. rodgers r j, ishii y, halford j c g, et al. orexins and appetite regulation. neuropeptides, 2002, 36(5): 303-325 .[2]. lang m, söll r m, dürrenberger f, et al. 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. journal of medicinal chemistry, 2004, 47(5): 1153-1160.[3]. bingham s, et al. orexin-a, an hypothalamic peptide with analgesic properties. pain, 2001, 92(1-2): 81-90.
storage
-20°C
Orexin A (bovine, human, mouse, rat) Preparation Products And Raw materials
Raw materials
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View Lastest Price from Orexin A (bovine, human, mouse, rat) manufacturers
- Product
- Orexin A Peptide(bovine, human, mouse, rat) 205640-90-0
- Price
- US $0.00/mg
- Min. Order
- 10mg
- Purity
- 99% min
- Supply Ability
- 20 tons
- Release date
- 2023-06-09
- Product
- Orexin A (bovine, human, mouse, rat) 205640-90-0
- Price
- US $7.00/KG
- Min. Order
- 1KG
- Purity
- 99%
- Supply Ability
- 100KG
- Release date
- 2020-02-13