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Nts

Official Full Name
neurotensin
Background
gene encodes a precursor protein for both peptides; neurotensin may be involved in smooth muscle contraction and possibly fat metabolism.
Synonyms
NTS; neurotensin; neurotensin/neuromedin N; neuromedin N; NN; NT; NT/N; NTS1; NMN-125; NN, NT, NT/N, NTS1, NMN-125

Neurotensin (NTS) is a peptide substance composed of 13 amino acid residues. Since it was first discovered in 1973, it has attracted much attention in many fields of biology and medicine. In the peripheral system, neurotensin mainly functions as a gastrointestinal hormone; in the central nervous system, neurotensin is a multifunctional neurotransmitter or neuromodulator and is associated with a variety of neuropsychiatric diseases. 

Neurotensin signalling in colorectal cancer cells. Figure 1. Neurotensin signalling in colorectal cancer cells. (Shengyang, Q., et al. 2017)

NTS and Receptors

So far, three subtypes of Neurotesin Receptors (NTRs) have been successfully cloned: NTR1, NTR2, and NTR3. In addition, a controversial fourth subtype: NTR4 has been discovered. The two receptor subtypes, NTR1 and NTR2, have been studied the most. In the central nervous system, neurotensin, as a multi-functional neurotransmitter or neuromodulator, mainly regulates dopamine, tryptophan, γ-aminobutyric acid, glutamic acid and the combination of NTR1 and NTR2. The function of the cholinergic system regulates the release of pituitary hormones, inhibits food intake, reduces spontaneous exercise, triggers analgesic effects insensitive to naloxone, and regulates stress-induced analgesia.

The overlapping of anatomical relationship between neurotensin, NTR1 and dopamine and dopamine D2 receptors makes them have a wide range of functional interactions at the cellular level. The study by St-Gelais et al. found that microinjection of neurotensin in the ventral tegmental area in the limbic system of the midbrain can directly increase the discharge of dopaminergic neurons projected into the nucleus accumbens. A recent animal experiment found that the level of dopamine and its metabolite dihydroxy-Phenyl Aceticacid (DOPAC) in the central striatum of neurotensin knockout mice is no different from normal mice. The difference in the above research results shows that the effect of neurotensin on dopamine release varies with the experimental model and the target brain area.

NTS and Intestinal Diseases

The etiology and pathogenesis of inflammatory bowel disease are currently not fully understood, and immune factors are one of its causes. In recent years, several laboratories have confirmed that the antigen-antibody reaction between NTS and its corresponding receptors in the intestinal mucosa can promote the occurrence of intestinal mucosal inflammation. The levels of NTS in the plasma and intestinal mucosa tissue of patients with ulcerative colitis are lower than that of the control group. NTS binds to NTR1 on the intestinal mucosa to produce biological effects on the intestine. Overexpression of NTR1 was found on the colonic mucosa of mice with experimental inflammatory bowel disease, and the number of NTR1 increased gradually. During the progression of inflammatory bowel disease to colon tumors, NTS and NTR1 have a two-way regulatory effect on colonic mucosal inflammation. Stimulating the production of cytokines and chemokines, between chronic mucosal inflammation and intestinal malignancies, NTS and NTR1 may become unique signals. It stimulates interleukin chemotaxis and leukocyte aggregation, and affects the progression of cancer (including colon cancer) through mitogenic, angiogenic, and single-gene effects.

NTS and Tumor

The study found that NTR1 is expressed in approximately 88% of pancreatic cancer xenografts, and the mRNA level of NTR1 is more highly expressed in advanced pancreatic cancer than early. In terms of pancreatic cancer cell invasion, NTS/NTR1 signaling can stimulate sodium-proton exchanger 1 (NHE1) by activating mitogen-and stress-activated kinase 1/2 (MSK1/2) and the phosphorylation of cAMP response element binding protein (CREB), which makes intracellular alkalization, extracellular acidification, and expression of interleukin 8 (interleukin, IL-8), thereby enhancing its invasion ability and its phenotype transfer. The expression of NTS increases the tumorigenic potential of prostate cancer. It was found that after long-term treatment with LNCaP cells by androgen inhibitors, the expression of NTS and its receptors increased, and the proliferation rate was accelerated, the cell cycle process was accelerated, and the invasive ability was increased, and this effect can be blocked by the siRNA of NTS. The study found that in primary prostate cancer cells, NTR1 is up-regulated in basal phenotype cells, while NTR2 and NTR3 are up-regulated in luminal phenotype cells, indicating that NTRs can be used as targets for the diagnosis of poorly and well differentiated prostate cancer.

References:

  1. Shengyang, Q. , Gianluca, P. , Francesca, F. , Shahnawaz, R. , Ara, D. , & Paris, T. , et al. (2017). A review of the role of neurotensin and its receptors in colorectal cancer. Gastroenterology Research & Practice, 2017, 1-8.
  2. Hashi, H. , Nakamura, Y. , Ishii, J. , & Kondo, A. . (2017). Modifying expression modes of human neurotensin receptor type 1 alters sensing capabilities for agonists in yeast signaling biosensor. Biotechnology Journal, 1700522.
  3. Nikolaou, S. , Qiu, S. , Fiorentino, F. , Simillis, C. , & Kontovounisios, C. . (2020). The role of neurotensin and its receptors in non-gastrointestinal cancers: a review. Cell Communication and Signaling, 18(1).

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