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Motilin (human, porcine)

Endogenous peptide regulator of gastrointestinal motility CAS# 52906-92-0

Motilin (human, porcine)

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Chemical structure

Motilin (human, porcine)

3D structure

Chemical Properties of Motilin (human, porcine)

Cas No. 52906-92-0 SDF Download SDF
PubChem ID 16129683 Appearance Powder
Formula C120H188N34O35S M.Wt 2699.07
Type of Compound N/A Storage Desiccate at -20°C
Solubility Soluble to 1 mg/ml in water
Sequence FVPIFTYGELQRMQEKERNKGQ
SMILES CCC(C)C(C(=O)NC(CC1=CC=CC=C1)C(=O)NC(C(C)O)C(=O)NC(CC2=CC=C(C=C2)O)C(=O)NCC(=O)NC(CCC(=O)O)C(=O)NC(CC(C)C)C(=O)NC(CCC(=O)N)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCSC)C(=O)NC(CCC(=O)N)C(=O)NC(CCC(=O)O)C(=O)NC(CCCCN)C(=O)NC(CCC(=O)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC(=O)N)C(=O)NC(CCCCN)C(=O)NCC(=O)NC(CCC(=O)N)C(=O)O)NC(=O)C3CCCN3C(=O)C(C(C)C)NC(=O)C(CC4=CC=CC=C4)N
Standard InChIKey LVRVABPNVHYXRT-UHFFFAOYSA-N
Standard InChI InChI=1S/C120H188N34O35S/c1-9-64(6)97(152-114(184)86-31-22-53-154(86)117(187)96(63(4)5)151-99(169)70(123)56-66-23-12-10-13-24-66)115(185)150-84(57-67-25-14-11-15-26-67)113(183)153-98(65(7)155)116(186)149-83(58-68-32-34-69(156)35-33-68)101(171)135-60-91(161)136-75(39-45-93(163)164)105(175)147-82(55-62(2)3)111(181)145-77(37-43-88(125)158)106(176)140-73(29-20-51-132-119(128)129)103(173)146-80(48-54-190-8)110(180)142-76(36-42-87(124)157)107(177)144-79(41-47-95(167)168)108(178)139-72(28-17-19-50-122)102(172)143-78(40-46-94(165)166)109(179)141-74(30-21-52-133-120(130)131)104(174)148-85(59-90(127)160)112(182)138-71(27-16-18-49-121)100(170)134-61-92(162)137-81(118(188)189)38-44-89(126)159/h10-15,23-26,32-35,62-65,70-86,96-98,155-156H,9,16-22,27-31,36-61,121-123H2,1-8H3,(H2,124,157)(H2,125,158)(H2,126,159)(H2,127,160)(H,134,170)(H,135,171)(H,136,161)(H,137,162)(H,138,182)(H,139,178)(H,140,176)(H,141,179)(H,142,180)(H,143,172)(H,144,177)(H,145,181)(H,146,173)(H,147,175)(H,148,174)(H,149,186)(H,150,185)(H,151,169)(H,152,184)(H,153,183)(H,163,164)(H,165,166)(H,167,168)(H,188,189)(H4,128,129,132)(H4,130,131,133)
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 Motilin (human, porcine)

DescriptionEndogenous motilin receptor ligand (Ki = 2.3 nM) that regulates gastrointestinal motor function. Stimulates contraction of gut smooth muscle (EC50 = 1 nM) and increases pepsin release.

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Background on Motilin (human, porcine)

Motilin(human, porcine) is an endogenous motilin receptor ligand with Ki and EC50 of 2.3 nM and 0.3 nM in a Chinese hamster ovary cell line. Sequence: Phe-Val-Pro-Ile-Phe-Thr-Tyr-Gly-Glu-Leu-Gln-Arg-Met-Gln-Glu-Lys-Glu-Arg-Asn-Lys-Gly-Gln.

In Vitro:[Bpa1,Ile13]motilin is a full agonist at the motilin receptor that increases intracellular calcium in a concentration-dependent manner (EC50 = 1.5 ± 0.4 nM)[1]. Motilin binds with high affinity (IC50 0.7± 0.2 nM) to receptors on smooth muscle cells. Motilin selectively activates G(q) and G(13), stimulates G alpha(q)-dependent phosphoinositide (PI) hydrolysis and 1,4,5-trisphosphate (IP(3))-dependent Ca2+ release, and increases cytosolic free Ca2+. Motilin induces a biphasic, concentration-dependent contraction (EC50 = 1.0 +/- 0.2 nM), consisting of an initial peak followed by a sustained contraction[2].

References:
[1]. Coulie B, et al. Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling. J Biol Chem. 2001 Sep 21;276(38):35518-22. Epub 2001 Jul 18. [2]. Huang J, et al. Signaling pathways mediating gastrointestinal smooth muscle contraction and MLC20 phosphorylation by motilin receptors. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G23-31.

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References on Motilin (human, porcine)

Signaling pathways mediating gastrointestinal smooth muscle contraction and MLC20 phosphorylation by motilin receptors.[Pubmed:15591586]

Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G23-31.

The signaling cascades initiated by motilin receptors in gastric and intestinal smooth muscle cells were characterized. Motilin bound with high affinity (IC(50) 0.7 +/- 0.2 nM) to receptors on smooth muscle cells; the receptors were rapidly internalized via G protein-coupled receptor kinase 2 (GRK2). Motilin selectively activated G(q) and G(13), stimulated G alpha(q)-dependent phosphoinositide (PI) hydrolysis and 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) release, and increased cytosolic free Ca(2+). PI hydrolysis was blocked by expression of G alpha(q) minigene and augmented by overexpression of dominant negative RGS4(N88S) or GRK2(K220R). Motilin induced a biphasic, concentration-dependent contraction (EC(50) = 1.0 +/- 0.2 nM), consisting of an initial peak followed by a sustained contraction. The initial Ca(2+)-dependent contraction and myosin light-chain (MLC)(20) phosphorylation were inhibited by the PLC inhibitor U-73122 and the MLC kinase inhibitor ML-9 but were not affected by the Rho kinase inhibitor Y27632 or the PKC inhibitor bisindolylmaleimide. Sustained contraction and MLC(20) phosphorylation were RhoA dependent and mediated by two downstream messengers: PKC and Rho kinase. The latter was partly inhibited by expression of G alpha(q) or G alpha(13) minigene and abolished by coexpression of both minigenes. Sustained contraction and MLC(20) phosphorylation were partly inhibited by Y27632 and bisindolylmaleimide and abolished by a combination of both inhibitors. The inhibition reflected phosphorylation of two MLC phosphatase inhibitors: CPI-17 via PKC and MYPT1 via Rho kinase. We conclude that motilin initiates a G alpha(q)-mediated cascade involving Ca(2+)/calmodulin activation of MLC kinase and transient MLC(20) phosphorylation and contraction as well as a sustained G alpha(q)- and G alpha(13)-mediated, RhoA-dependent cascade involving phosphorylation of CPI-17 by PKC and MYPT1 by Rho kinase, leading to inhibition of MLC phosphatase and sustained MLC(20) phosphorylation and contraction.

Identification of peptide ligand-binding domains within the human motilin receptor using photoaffinity labeling.[Pubmed:11461914]

J Biol Chem. 2001 Sep 21;276(38):35518-22.

The cDNA encoding the human motilin receptor was recently cloned and found to represent a G protein-coupled receptor that is structurally related to the growth hormone secretagogue receptors. Together, these represent a new Class I receptor family. Our aim in the present work is to gain insight into the molecular basis of binding of motilin to its receptor using photoaffinity labeling. To achieve this, we developed a Chinese hamster ovary cell line that overexpressed functional motilin receptor (CHO-MtlR; 175,000 sites per cell, with K(i) = 2.3 +/- 0.4 nm motilin and EC(50) = 0.3 +/- 0.1 nm motilin) and a radioiodinatable peptide analogue of human motilin that incorporated a photolabile p-benzoyl-l-phenylalanine (Bpa) residue into its pharmacophoric domain. This probe, [Bpa(1),Ile(13)]motilin, was a full agonist at the motilin receptor that increased intracellular calcium in a concentration-dependent manner (EC(50) = 1.5 +/- 0.4 nm). This photolabile ligand bound specifically and with high affinity to the motilin receptor (K(i) = 12.4 +/- 1.0 nm), and covalently labeled that molecule within its M(r) = 45,000 deglycosylated core. Cyanogen bromide cleavage demonstrated its covalent attachment to fragments of the receptor having apparent M(r) = 6,000 and M(r) = 31,000. These were demonstrated to represent fragments that included both the first and the large second extracellular loop domains, with the latter representing a unique structural feature of this receptor. The spatial approximation of the pharmacophoric domain of motilin with these receptor domains support their functional importance as well.

Motilin and clinical application.[Pubmed:9210180]

Peptides. 1997;18(4):593-608.

Motilin is a regulatory polypeptide of 22 amino acid residues and orginates in motilin cells scattered in the duodenal epithelium of most mammals and chickens. Motilin is released into the general circulation at about 100-min intervals during the interdigestive state and is the most important factor in controlling the interdigestive migrating contractions. Recent studies have revealed that motilin stimulates endogenous release of the endocrine pancreas. Clinical application of motilin as a prokinetic has become possible since erythromycin and its derivatives were proved to be nonpeptide motilin agonists.

Description

Motilin (26-47), human, porcine is an endogenous motilin receptor ligand with Ki and EC50 of 2.3 nM and 0.3 nM in a Chinese hamster ovary cell line.

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