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Neurotensin (NT) is an endogenous tridecapeptide neurotransmitter (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-pro-Tyr-Ile-Leu-OH) that was originally isolated from bovine hypothalamus. NT influences distinct central and peripheral physiological functions in mammals. Central administration of NT modulates dopaminergic transmission and triggers hypothermic and naloxone-insensitive analgesic responses, whereas peripheral effects include hypotension, decrease gastric acid release, potentiation of lipid digestion. NT causes contraction of smooth muscle. NT is widely distributed throughout the CNS. It has been localized to catecholamine-containing neurons. NT gene (human chromosome 12q21) produces both NT and neuromedin N (NN). In the rat, the NT precursor consists of a 169-aa polypeptide. The signal peptide (1-22 aa) is removed to produce a peptide that is further processed to produce NN (142-147 aa) and NT (150-162 aa). NT sequence is completely conserved in mouse, rat, human, canine, bovine etc. NT initiates its biological action by interacting with two distinct G-protein coupled receptors (NTR1 and NTR2). Recently, a third receptor NTR3 has been identified that is identical to gp95/sortilin and it is not coupled via the G-proteins. All three receptors bind NT through its C-terminal hexapeptide sequence (8 RRPYIL 13). Biologically active NT (NT8-13) has also been shown to interact with the extracellular domain 3 (between TM6-7) of NTR1.

NTR1/NTRH/NTSR1/NT1 (mouse/rat 424 aa; human 418 aa, chromosome 20q1; ~84% interspecies sequence homology) is the levocabastine-insensitive, high affinity receptor for NT. It has the typical structure of GPCR: 7 TM domains with extracellular N-terminus and cytoplasmic C-terminus. It is shown to mediate a number of peripheral and central NT responses, including the neuroleptic-like effects of the peptide. It is highly expressed in the brain, small intestine, and other peripheral tissues.
NTR2/NTRL/NTSR2/NT2 (mouse 417 aa, rat 416 aa; human 410 aa, chromosome 20q1; ~75% interspecies sequence homology) also binds NT. Unlike NTR-1, NTR-2 recognizes, with high affinity, levocabastine, and histamine H1 receptor antagonist previously shown to compete with NT for low-affinity binding sites in brain. NTR2 is ~40 identical with NTR1. It has been suggested that the most prominent biological effects, analgesia and hypothermia, are mediated by NTR2. A non-peptide NT-antagonist SR 48692m which preferentially recognizes the NTR1, did not antagonize these effects. In mouse, it is maximally expressed the cerebellum, hippocampus, and neocortex. Low levels are also found in heart and intestine.

Most recently, a novel, non-GPCR, NTR3/sortilin/gp95/NT3 (mouse 825 aa, rat 748 aa; human 833 aa, chromosome 1p21.3; ~92% identity between human and mouse) also binds NT. Sortilin was initially isolated as by its affinity for receptor-associated protein (RAP). NTR3, the first non-GPCR neuropeptides receptor, sequence includes a putative secretory signal peptide, a furin cleavage site, and a single transmembrane domain near the C-terminus. The mature protein has 44 N-terminal residues removed during processing. It is homologous to the yeast protein Vps10p and the human sortilin-related receptor. The C terminus of the protein contains a lysosomal sorting motif shared by the mannose-6-phosphate receptors. NTR3 is expressed at high levels in brain, spinal cord, heart, skeletal muscle, thyroid, placenta, and testis.

ADI has produced antibodies to NT and NTR1-3 using peptide sequences specific for each protein. The appropriate control immunogenic peptides are also available to confirm specificity of antibodies.

m=mouse; r=rat; h=human; b=bovine; d=dog; ~CT or ~NT=near C or N-terminus. EC=Extracellular; CP=Cytoplasmic domain; Control peptides (unconjugated, free, antigenic peptides), because of their small size, are not recommended for Western. They should be used in ELISA/antibody blocking studies.

"Neat Antisera" are the unpurified antiserum and it is suitable for ELISA and Western.
"Affinity pure" IgG may be more suitable for immunohistochemical applications and to reduce background in most immunological applications.
"Control peptides" can not be used for Western as they are very short peptides. They are intended for ELISA or antibody blocking studies to establish antibody specificity.

All Products are for in vitro research use only.

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