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Neuromedin S (rat)

Potent, endogenous NMU1 and NMU2 agonist CAS# 843782-19-4

Neuromedin S (rat)

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Chemical structure

Neuromedin S (rat)

3D structure

Chemical Properties of Neuromedin S (rat)

Cas No. 843782-19-4 SDF Download SDF
PubChem ID 131954574 Appearance Powder
Formula C193H307N57O49S M.Wt 4241.97
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 0.50 mg/ml in 20% acetonitrile / water
Sequence LPRLLHTDSRMATIDFPKKDPTTSLGRPFFLFRPRN

(Modifications: Asn-36 = C-terminal amide)

Chemical Name 4-[[1-[2-[[6-amino-1-[[6-amino-1-[[1-[2-[[1-[[1-[[1-[[1-[[2-[[5-carbamimidamido-1-[2-[[1-[[1-[[1-[[1-[[5-carbamimidamido-1-[2-[[5-carbamimidamido-1-[(1,4-diamino-1,4-dioxobutan-2-yl)amino]-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-3-carboxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[2-[[2-[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[1-(2-amino-4-methylpentanoyl)pyrrolidine-2-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylpentanoyl]amino]-4-methylpentanoyl]amino]-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxybutanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-4-methylsulfanylbutanoyl]amino]propanoylamino]-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoic acid
SMILES CCC(C)C(C(=O)NC(CC(=O)O)C(=O)NC(CC1=CC=CC=C1)C(=O)N2CCCC2C(=O)NC(CCCCN)C(=O)NC(CCCCN)C(=O)NC(CC(=O)O)C(=O)N3CCCC3C(=O)NC(C(C)O)C(=O)NC(C(C)O)C(=O)NC(CO)C(=O)NC(CC(C)C)C(=O)NCC(=O)NC(CCCNC(=N)N)C(=O)N4CCCC4C(=O)NC(CC5=CC=CC=C5)C(=O)NC(CC6=CC=CC=C6)C(=O)NC(CC(C)C)C(=O)NC(CC7=CC=CC=C7)C(=O)NC(CCCNC(=N)N)C(=O)N8CCCC8C(=O)NC(CCCNC(=N)N)C(=O)NC(CC(=O)N)C(=O)N)NC(=O)C(C(C)O)NC(=O)C(C)NC(=O)C(CCSC)NC(=O)C(CCCNC(=N)N)NC(=O)C(CO)NC(=O)C(CC(=O)O)NC(=O)C(C(C)O)NC(=O)C(CC9=CNC=N9)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCCNC(=N)N)NC(=O)C1CCCN1C(=O)C(CC(C)C)N
Standard InChIKey SKSKHLKOZPRFOV-UHFFFAOYSA-N
Standard InChI InChI=1S/C193H307N57O49S/c1-19-104(12)149(241-182(293)152(108(16)255)242-155(266)105(13)217-157(268)121(66-79-300-18)221-159(270)118(56-36-69-210-189(199)200)220-172(283)137(96-251)239-170(281)134(92-147(261)262)236-180(291)150(106(14)253)243-171(282)132(89-114-94-209-98-216-114)233-165(276)128(84-103(10)11)229-163(274)126(82-101(6)7)228-161(272)120(58-38-71-212-191(203)204)224-174(285)139-61-41-74-246(139)184(295)115(196)80-99(2)3)179(290)235-133(91-146(259)260)169(280)237-135(88-113-52-30-23-31-53-113)187(298)249-77-44-63-141(249)176(287)222-117(55-33-35-68-195)158(269)219-116(54-32-34-67-194)162(273)238-136(93-148(263)264)188(299)250-78-45-65-143(250)178(289)244-153(109(17)256)183(294)245-151(107(15)254)181(292)240-138(97-252)173(284)227-125(81-100(4)5)156(267)215-95-145(258)218-122(59-39-72-213-192(205)206)185(296)247-75-43-64-142(247)177(288)234-131(87-112-50-28-22-29-51-112)168(279)232-130(86-111-48-26-21-27-49-111)167(278)230-127(83-102(8)9)164(275)231-129(85-110-46-24-20-25-47-110)166(277)225-123(60-40-73-214-193(207)208)186(297)248-76-42-62-140(248)175(286)223-119(57-37-70-211-190(201)202)160(271)226-124(154(198)265)90-144(197)257/h20-31,46-53,94,98-109,115-143,149-153,251-256H,19,32-45,54-93,95-97,194-196H2,1-18H3,(H2,197,257)(H2,198,265)(H,209,216)(H,215,267)(H,217,268)(H,218,258)(H,219,269)(H,220,283)(H,221,270)(H,222,287)(H,223,286)(H,224,285)(H,225,277)(H,226,271)(H,227,284)(H,228,272)(H,229,274)(H,230,278)(H,231,275)(H,232,279)(H,233,276)(H,234,288)(H,235,290)(H,236,291)(H,237,280)(H,238,273)(H,239,281)(H,240,292)(H,241,293)(H,242,266)(H,243,282)(H,244,289)(H,245,294)(H,259,260)(H,261,262)(H,263,264)(H4,199,200,210)(H4,201,202,211)(H4,203,204,212)(H4,205,206,213)(H4,207,208,214)
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 Neuromedin S (rat)

DescriptionPotent, endogenous neuromedin U receptor agonist (EC50 values are 65 and 91 pM at NMU1 and NMU2 respectively). Induces phase shifts in the circadian rhythm of locomotor activity following i.c.v. administration. Potent endogenous anorexigenic peptide.

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References on Neuromedin S (rat)

Different distribution of neuromedin S and its mRNA in the rat brain: NMS peptide is present not only in the hypothalamus as the mRNA, but also in the brainstem.[Pubmed:23264767]

Front Endocrinol (Lausanne). 2012 Dec 3;3:152.

Neuromedin S (NMS) is a neuropeptide identified as another endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1, which have also been identified as types 1 and 2 receptors for neuromedin U structurally related to NMS. Although expression of NMS mRNA is found mainly in the brain, spleen, and testis, the distribution of its peptide has not yet been investigated. Using a newly prepared antiserum, we developed a highly sensitive radioimmunoassay for rat NMS. NMS peptide was clearly detected in the rat brain at a concentration of 68.3 +/- 3.4 fmol/g wet weight, but it was hardly detected in the spleen and testis. A high content of NMS peptide was found in the hypothalamus, midbrain, and pons-medulla oblongata, whereas abundant expression of NMS mRNA was detected only in the hypothalamus. These differing distributions of the mRNA and peptide suggest that nerve fibers originating from hypothalamic NMS neurons project into the midbrain, pons, or medulla oblongata. In addition, abundant expression of type 2 receptor mRNA was detected not only in the hypothalamus, but also in the midbrain and pons-medulla oblongata. These results suggest novel, unknown physiological roles of NMS within the brainstem.

Neuromedin S increases L-type Ca(2+) channel currents through G(i)alpha-protein and phospholipase C-dependent novel protein kinase C delta pathway in adult rat ventricular myocytes.[Pubmed:22832358]

Cell Physiol Biochem. 2012;30(3):618-30.

Neuromedin S (NMS), a peptide structurally related to NMU, has been identified in the mammalian heart tissues. However to date, any role of NMS in cardiomyocytes and the relevant mechanisms still remain unknown. In this study, we identified a novel functional role of NMS in modulating L-type Ca(2+) channels in adult rat ventricular myocytes, in which NMU type 2 receptors (NMUR2), but not NMUR1, are endogenously expressed. We found that NMS at 0.1 microM reversibly increased I(Ba) by ~29.7%. Intracellular infusion of GDP-beta-S or a selective antibody raised against the G(i)-protein blocked the stimulatory effects of NMS. The classical and novel protein kinase C (nPKC) antagonist calphostin C or chelerythrine chloride, as well as the phospholipase C (PLC) inhibitor U73122, abolished NMS responses, whereas a classical PKC antagonist Go6976 or a PKA antagonist PKI 5-24 had no such effects. Pretreatment of cells with PKC-delta specific inhibitor rottlerin or intracellular application of a PKC-delta-derived inhibitory peptide, deltaV1-1, abolished NMS responses, while an inactive control peptide had no effects. In summary, NMS acting through NMUR2 increases I(Ba) via a G(i)alpha-protein-dependent PKC-delta pathway in rat ventricular myocytes.

Emerging pharmacology and physiology of neuromedin U and the structurally related peptide neuromedin S.[Pubmed:19519756]

Br J Pharmacol. 2009 Sep;158(1):87-103.

Neuromedin U (NMU) has been paired with the G-protein-coupled receptors (GPRs) NMU(1) (formerly designated as the orphan GPR66 or FM-3) and NMU(2) (FM-4 or hTGR-1). Recently, a structurally related peptide, neuromedin S (NMS), which shares an amidated C-terminal heptapeptide motif, has been identified in both rat and human, and has been proposed as a second ligand for these receptors. Messenger RNA encoding NMU receptor subtypes shows differential expression: NMU(1) is predominantly expressed in peripheral tissues, particularly the gastrointestinal tract, whereas NMU(2) is abundant within the brain and spinal cord. NMU peptide parallels receptor distribution with highest expression in the gastrointestinal tract and specific structures within the brain, reflecting its major role in the regulation of energy balance. The NMU knockout mouse has an obese phenotype and, in agreement, the Arg165Trp amino acid variant of NMU-25 in humans, which is functionally inactive, co-segregated with childhood-onset obesity. Emerging physiological roles for NMU include vasoconstriction mediated predominantly via NMU(1) with nociception and bone remodelling via NMU(2). The NMU system has also been implicated in the pathogenesis of septic shock and cancers including bladder carcinoma and acute myeloid leukaemia. Intriguingly, NMS is more potent at NMU(2) receptors in vivo where it has similar central actions in suppression of feeding and regulation of circadian rhythms to NMU. Taken together with its vascular actions, NMU may be a functional link between energy balance and the cardiovascular system and may provide a future target for therapies directed against the disorders that comprise metabolic syndrome.

Neuromedin s is a novel anorexigenic hormone.[Pubmed:15976061]

Endocrinology. 2005 Oct;146(10):4217-23.

A novel 36-amino acid neuropeptide, neuromedin S (NMS), has recently been identified in rat brain and has been shown to be an endogenous ligand for two orphan G protein-coupled receptors, FM-3/GPR66 and FM-4/TGR-1. These receptors have been identified as neuromedin U (NMU) receptor type 1 and type 2, respectively. In this study, the physiological role of the novel peptide, NMS, on feeding regulation was investigated. Intracerebroventricular (icv) injection of NMS decreased 12-h food intake during the dark period in rats. This anorexigenic effect was more potent and persistent than that observed with the same dose of NMU. Neuropeptide Y, ghrelin, and agouti-related protein-induced food intake was counteracted by coadministration of NMS. Icv administration of NMS increased proopiomelanocortin mRNA expression in the arcuate nucleus (Arc) and CRH mRNA in the paraventricular nucleus (PVN). Pretreatment with SHU9119 (antagonist for alpha-MSH) and alpha-helical corticotropin-releasing factor-(9-41) (antagonist for CRH) attenuated NMS-induced suppression of 24-h food intake. After icv injection of NMS, Fos-immunoreactive cells were detected in both the PVN and Arc. When neuronal multiple unit activity was recorded in the PVN before and after icv injection of NMS, a significant increase in firing rate was observed 5 min after administration, and this increase continued for 100 min. These results suggest that the novel peptide, NMS, may be a potent anorexigenic hormone in the hypothalamus, and that expression of proopiomelanocortin mRNA in the Arc and CRH mRNA in the PVN may be involved in NMS action on feeding.

Identification of neuromedin S and its possible role in the mammalian circadian oscillator system.[Pubmed:15635449]

EMBO J. 2005 Jan 26;24(2):325-35.

The discovery of neuropeptides has resulted in an increased understanding of novel regulatory mechanisms of certain physiological phenomena. Here we identify a novel neuropeptide of 36 amino-acid residues in rat brain as an endogenous ligand for the orphan G protein-coupled receptor FM-4/TGR-1, which was identified to date as the neuromedin U (NMU) receptor, and designate this peptide 'neuromedin S (NMS)' because it is specifically expressed in the suprachiasmatic nuclei (SCN) of the hypothalamus. NMS shares a C-terminal core structure with NMU. The NMS precursor contains another novel peptide. NMS mRNA is highly expressed in the central nervous system, spleen and testis. In rat brain, NMS expression is restricted to the core of the SCN and has a diurnal peak under light/dark cycling, but remains stable under constant darkness. Intracerebroventricular administration of NMS in rats activates SCN neurons and induces nonphotic type phase shifts in the circadian rhythm of locomotor activity. These findings suggest that NMS in the SCN is implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.

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