NEUROTENSIN
Structure Gene, mRNA, and precursor Synthesis and release Clinical implications Receptors Signal transduction pathway Biological functions- Product Name
- NEUROTENSIN
- CAS No.
- 39379-15-2
- Chemical Name
- NEUROTENSIN
- Synonyms
- NEUROTENSIN;PYR-LYENKPRRPYIL;NEUROTENSIN (1-13);NEUROTENSIN, BOVINE;M.W. 1672.92 C78H121N21O20;NEUROTENSIN (HUMAN, BOVINE, CANINE);NEUROTENSIN (HUMAN, BOVINE, CANINE) 2ACOH 6H2O;Inhibitor,Neurotensin Receptor,Neurotensin,inhibit;PYR-LEU-TYR-GLU-ASN-LYS-PRO-ARG-ARG-PRO-TYR-ILE-LEU;GLP-LEU-TYR-GLU-ASN-LYS-PRO-ARG-ARG-PRO-TYR-ILE-LEU
- CBNumber
- CB2118390
- Molecular Formula
- C78H121N21O20
- Formula Weight
- 1672.92
- MOL File
- 39379-15-2.mol
NEUROTENSIN Property
- RTECS
- QQ4482000
- storage temp.
- Desiccate at -20°C
- solubility
- insoluble in EtOH; ≥15.33 mg/mL in DMSO; ≥22.55 mg/mL in H2O
- form
- Lyophilized powder.
- color
- White to off-white
- Water Solubility
- Soluble to 0.70 mg/ml in water
- Sequence
- Pyr-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH
N-Bromosuccinimide Price
- Product number
- 05-23-1200
- Product name
- Neurotensin - CAS 39379-15-2 - Calbiochem
- Purity
- Potent hypothalamic peptide neurotransmitter.
- Packaging
- 5MG
- Price
- $245
- Updated
- 2023/06/20
- Product number
- J66243
- Product name
- Neurotensin, guinea pig
- Packaging
- 25mg
- Price
- $527
- Updated
- 2023/06/20
- Product number
- J66243
- Product name
- Neurotensin, guinea pig
- Packaging
- 10mg
- Price
- $198
- Updated
- 2021/12/16
- Product number
- 1909
- Product name
- Neurotensin
- Packaging
- 1
- Price
- $87
- Updated
- 2021/12/16
- Product number
- N391000
- Product name
- Neurotensin
- Packaging
- 1mg
- Price
- $145
- Updated
- 2021/12/16
NEUROTENSIN Chemical Properties,Usage,Production
Structure
Neurotensin and neuromedin N (NMN) are synthesized by a common precursor (pro-NT/NMN). Human
pro-NT/NMN consists of a conserved polypeptide of
170 aa residues starting with a signal peptide of 23 aa residues. Four lysine-arginine cleavage sites are
located in the C-terminal position of pro-NT/NMN. NT is a tridecapeptide with a highly conserved
C-terminal portion (8–13) that is responsible for its biological activities. NT peptides have been identified in various vertebrates except for cyclostomes and
elasmobranchs. NMN and the frog skin peptide, xenopsin, exhibit strong similarity with the C-terminal portion
of NT. Human, rat, and mouse: Mr 1671.9; pI 8.6. Soluble in
water and 5% acetic acid.
Gene, mRNA, and precursor
The human NT/NMN gene is located on chromosome 12q21 and its mRNA has 1264 bp. The gene encompasses 8.7 kb and is divided into four exons by three introns. The fourth exon encodes both NT and NMN. NT/NMN mRNA or protein is detected in the central nervous system (hypothalamus, pituitary, forebrain) and gastrointestinal tract (predominantly in the small intestinal mucosa) of a variety of tetrapods. NT is also detected in the adrenal medulla of mammals. Two distinct mRNAs, 1.0 and 1.5 kb in size, are present in the central nervous system and intestine of the rat.2 The smaller mRNA is predominantly expressed in the intestine and anterior pituitary while both mRNAs are expressed equally in the hypothalamus, brainstem, and cortex.
Synthesis and release
The regulation of NT/NMN gene transcription depends on specific cis-regulatory elements located in the proximal 50 flanking region of the gene. The cis-regulatory element of the human NT/NMN gene contains a CRE/AP-1-like element that binds both AP-1 and CREB/ATF proteins, the glucocorticoid response element (GRE), and the AP-1 site. NT/NMN gene expression and NT peptide synthesis are also induced in response to combined treatment with nerve growth factor, dexamethasone, lithium, and the adenylate cyclase activator forskolin. In the hypothalamus and anterior pituitary, depolarization by high K+ concentration causes the release of NT and NMN from synaptic vesicles or secretory granules in a Ca2+-dependent manner. In the gastrointestinal tract, NT is released in response to increased intraluminal fats.
Clinical implications
NT is related to the pathophysiology of a series of disorders, such as schizophrenia, drug abuse, Parkinson’s disease (PD), feeding disorders, cancer, cerebral stroke, and other neurodegenerative diseases. Furthermore, NT is involved in the physiology of pain induction, the central control of blood pressure, and inflammation. The levels of endogenous NT and NTR expression are decreased in patients with symptoms of schizophrenia. The number of NT binding sites and expression levels of NTR1 mRNA were decreased in the substantia nigra of patients with PD. NT and its analog NT69L reduce body weight and food intake in healthy and obese rats. The expression of NT is increased in the hypothalamus of anorexic animals. NT has potential as a therapeutic drug in feeding disorders. NT shows possible implications in cancer; the size of the colon or lung tumors increases in the presence of NT and becomes smaller in the presence of NTR1 antagonists. In cystic fibrosis patients with pancreatic insufficiency, the plasma concentration of NT is significantly increased compared with healthy controls. The high expression of NT receptors has potential as a useful marker for diagnosis and assessing the progression of pancreatic cancers, although plasma NT levels do not differ between healthy controls and pancreatic cancer patients. Many EIA kits for the measurement of plasma NT are sold by various companies (e.g., Peninsula Laboratories, Phoenix Pharmaceuticals, and Bachem).
Receptors
Three NT receptors, termed NTR1, NTR2, and NTR3 , have been identified. Both NTR1 and NTR2 are seven-transmembrane-spanning, G-proteincoupled receptors. Rat and human NTR1s consist of 424 and 418 aa residues, respectively. The human NTR1 gene is located at the long arm (20q13) of chromosome 20 and three introns in the coding regions. Rodent and human NTR2s (416 and 410 aa residues, respectively) share only around 40% amino acid identities with NTR1s. NTR2 has a shorter N-terminal extracellular tail and a longer third intracytoplasmic loop than NTR1. NTR3, also known as sortilin, belongs to a new receptor family sharing an N-terminal luminal domain related to the yeast sorting receptor Vps10p, which includes a single transmembrane domain. The human NTR3 gene encodes a protein of 833 aa residues. The cyclic C-terminal NT (8–13) analog binds human NTR1 and NTR2 with high affinity. Four NT analogs (Eisai compound, NT66L, NT67L, and NT69) and the highly selective NTR1 agonist PD149163 have antipsychotic efficacy. The nonpeptide NT antagonist SR 48692 has higher affinity for NTR1 (IC50=5.6nM) than for NTR2 (IC50=300nM) and inhibits several of the central and peripheral effects of NT. SR 142948A has high affinity for NTR1 and NTR2. SR 142948A is able to antagonize a more diverse array of NT-induced effects compared to SR 48692.
Signal transduction pathway
NTR1 has high affinity for NT and activates PKC, stimulating IP3 production through the Gq/11-coupled pathway. NTR1 is also linked to the Gs-mediated pathway, which increases intracellular cAMP levels. The affinity of NT for NTR2 is lower than that for NTR1. Human NTR2 is coupled to the Gq/11-dependent phospholipase C signal pathway, but not to Gs. Human NTR2 also interacts with Gi/o and G12/13. NTR3 activates the IP3-PKC signaling pathway in HT29 cells.
Biological functions
NT was first isolated based on hypotensive action and peripheral vasodilation.1 In the central nervous system, NT exerts various CNS effects, including hypothermia, analgesia, modulation of dopamine neurotransmission, stimulation of anterior pituitary hormone (ACTH, CRH, DA, GnRH, and SS) release, central control of blood pressure, inhibition of food intake, and sleep-wake regulation. In the gastrointestinal tract, NT exerts the effects of pancreatic endocrine secretion and colonic motility, and a decrease in gastric acid secretion.
Description
Neurotensin, a hypotensive peptide first isolated from the bovine hypothalamus, neurotensin acts as a neurotransmitter and neurotransmodulator in the central nervous system, and also as a local hormone in the small intestine. Neurotensin (NT) is a tridecapeptide that was originally isolated from extracts of the bovine hypothalamus in 1973, based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats.
Uses
Neurotensin is a selective, non-competitive NMDA receptor antagonist.
Definition
ChEBI: Neurotensin is a 13 amino acid peptide hormone which is found in the central nervous system and the gastrointestinal tract. It behaves as a neurotransmitter in the brain, as a hormone in the gut, and also as a neuromodulator. It is implicated in the pathophysiology of several CNS disorders (including schizophrenia, Parkinson's disease, drug abuse, pain, cancer, inflammation, eating disorders and central control of blood pressure) due to its association with a wide variety of neurotransmitter systems such as dopaminergic, sertonergic, glutamatergic, GABAergic, and cholinergic systems. It has a role as a human metabolite, a mitogen, a neurotransmitter and a vulnerary. It is a conjugate base of a neurotensin(1+).
in vitro
due to nt/ntr1 signaling potentiates expression of mir-133α, the mechanism of nt-regulated mir-133α expression and examining the role of mir-133α in intracellular ntr1 trafficking in human ncm460 colonocytes are very important. the negative transcription regulator (zinc finger e-box binding homeobox 1) is involved in nt-induced mir-133α upregulation. a binding target of mir-133α (silencing of mir-133α or overexpression of aftiphilin (aftph)) lowered ntr1 trafficking to plasma membrane in human colonocytes without affecting ntr1 internalization. aftph to early endosomes and the trans-golgi network (tgn) were localized in unstimulated human colonic epithelial cells. ntr1 localization was reduced by aftph overexpression in early endosomes. at the same time, it also increased expression of proteins related to endosomes and the tgn trafficking pathway. ntr1 expression was increased by aftph overexpression and de-acidification of intracellular vesicles. these results suggest a novel mechanism of gpcr trafficking in human colonic epithelial cells accounts for why a microrna, mir-133α regulates ntr1 trafficking through its downstream target aftph.
storage
Store at -20°C
References
[1]. law ik, jensen d, bunnett nw, pothoulakis c. neurotensin-induced mir-133α expression regulates neurotensin receptor 1 recycling through its downstream target aftiphilin. sci rep. 2016 feb 23;6:22195.
NEUROTENSIN Preparation Products And Raw materials
Raw materials
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