Neurotensin
neurotensin | ||||||
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Location (UCSC) | n/a | n/a | ||||
PubMed search | n/a | n/a |
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Neurotensin/neuromedin N precursor | |||||||||
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Symbol | Pro-NT_NN | ||||||||
Pfam | PF07421 | ||||||||
InterPro | IPR008055 | ||||||||
OPM superfamily | 257 | ||||||||
OPM protein | 2oyv | ||||||||
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Properties | |
C78H121N21O20 | |
Molar mass | 1672.92 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Neurotensin is a 13
Neurotensin is distributed throughout the central nervous system, with highest levels in the hypothalamus, amygdala and nucleus accumbens. It induces a variety of effects, including analgesia, hypothermia and increased locomotor activity. It is also involved in regulation of dopamine pathways. In the periphery, neurotensin is found in enteroendocrine cells of the small intestine, where it leads to secretion and smooth muscle contraction.[2]
Sequence and biosynthesis
Neurotensin shares significant sequence similarity in its 6
The sequence of bovine neurotensin was determined to be pyroGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH.
Clinical significance
Neurotensin is a potent mitogen for colorectal cancer.[6]
Neurotensin has been implicated in the modulation of
Neurotensin is an endogenous neuropeptide involved in
Gene expression
Neurotensin gene expression has been shown to be modulated by estrogen in both human SK-N-SH neuroblastoma cell cultures as well as in mice through interactions with cyclic AMP (cAMP) signaling. Specifically, estrogen increased cAMP activity and cAMP response element-binding protein phosphorylation in neuroblastoma cells prior to the induction of neurotensin gene transcription. Additionally, neurotensin gene transcription was blocked in knock-out mice lacking the RIIβ subunit of the protein kinase A holoenzyme. These findings may indicate mechanisms of cross-talk signaling in brain hormone activity and expression of hormone-related genes.[10] Other sex hormone-related changes in neurotensin expression have been associated with activity in the preoptic area. In female rats, neurotensin expression was shown to be at its highest in the medial preoptic area (mPOA) during the proestrus phase of the estrous cycle.[11]
Altered expression of neurotensin genes as well as neurotensin receptor genes have been exhibited in postpartum female mice. While neurotensin receptor 1 (Ntsr1) mRNA in the paraventricular nucleus of the hypothalamus (PVN) was lowered, neurotensin, but not neurotensin mRNA, was shown to be higher in the PVN. Neurotensin mRNA as well as the peptide itself were also expressed higher in the medial preoptic area (mPOA). These expression patterns were not shown in the virgin female control group, and align with other research implicating neurotensin gene expression variation in the regulation of maternal behaviors.[12]
Other patterns of neurotensin expression related to the medial preoptic area show relation to the modulation of social reward. Analysis of neurotensin gene-labelled neurons revealed that neurotensin-containing neuronal projections from the mPOA to the ventral tegmental area (VTA) in mice were associated with the encoding of odor cues as well as social attraction, further implicating neurotensin in hormonal as well as reward signaling.[13]
Neurotensin has also been implicated in learning processes. A study examining song development in male zebra finches showed variations in neurotensin and neurotensin receptor gene expression across different stages of song development. The early stage of transition between sensory and sensorimotor periods was marked by decreases in both neurotensin and neurotensin receptor mRNA expression, which may indicate a role of neurotensin in initiating sensorimotor learning. During the sensorimotor subsong stage, neurotensin gene expression and neurotensin receptor 1 (Ntsr1) gene expression exhibited complementary expression patterns in song-related brain regions, which may indicate changes in neuronal responses to neurotensin across development.[14]
Neurotensin also plays a role in peripheral tissues outside of the nervous system, mainly in the gastrointestinal tract, and has been implicated in cancer development. DNA promoter methylation has been shown to be a major regulator in the expression of neurotensin receptor 1 and 2 genes in colorectal cancer cells. Additionally, knock-down of the NTSR1 gene as well as treatment with a NTSR1 antagonist inhibited colorectal cancer cell proliferation and migration.[15] Leiomyomas or fibroid tumors in uterine tissue have also been associated with higher expression of neurotensin and NTSR1.[16]
See also
References
- PMID 4745447.
- PMID 11811984.
- PMID 1167549.
- PMID 3472221.
- PMID 2832414.
- PMID 17000667.
- S2CID 15095566.)
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: CS1 maint: multiple names: authors list (link - PMID 11427716.)
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: CS1 maint: multiple names: authors list (link - S2CID 41533372.
- PMID 9712639.
- PMID 11416022.
- PMID 24416154.
- PMID 28135243.
- PMID 29569407.
- PMID 28498396.
- PMID 20592307.
External links
- Neurotensin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Saplakoglu, Yasemin (2022-09-07). "A Good Memory or a Bad One? One Brain Molecule Decides". Quanta Magazine.