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Neurotensin is a 13 amino acid neuropeptide that is implicated in the regulation of luteinizing hormone and prolactin release and has significant interaction with the dopaminergic system. Neurotensin was first isolated from extracts of Cattle hypothalamus based on its ability to cause a visible vasodilation in the exposed cutaneous regions of anesthetized rats.
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 hyperlocomotion. 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 Pancreas and Bile secretion, reduced gastric acid secretion, and smooth muscle contraction.
The sequence of bovine neurotensin was determined to be pyroGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH. Neurotensin is synthesized as part of a 169 or 170 amino acid precursor protein that also contains the related neuropeptide neuromedin N. The peptide coding domains are located in tandem near the carboxyl terminal end of the precursor and are bounded and separated by paired basic amino acid (lysine-arginine) processing sites.
Neurotensin also appears to influence learning processes. In male zebra finches, expression of neurotensin and its receptor genes varies during song development. Both neurotensin and neurotensin receptor mRNA levels decrease during the transition from the sensory to sensorimotor phases of development, implicating neurotensin in the onset of sensorimotor learning. Later in development, neurotensin and neurotensin receptor 1 (Ntsr1) show complementary expression patterns in song-related brain regions, suggesting dynamic modulation of neural responses.
In peripheral tissues, neurotensin is predominantly expressed in the gastrointestinal tract, where it participates in digestion and local signaling. Its aberrant expression has also been associated with tumorigenesis.
Neurotensin is a potent mitogen for colorectal cancer.
Neurotensin has been implicated in the modulation of dopamine signaling, and produces a spectrum of pharmacological effects resembling those of antipsychotic drugs, leading to the suggestion that neurotensin may be an endogenous neuroleptic. Neurotensin-deficient mice display defects in responses to several antipsychotic drugs consistent with the idea that neurotensin signaling is a key component underlying at least some antipsychotic drug actions. These mice exhibit modest defects in prepulse inhibition (PPI) of the startle reflex, a model that has been widely used to investigate antipsychotic drug action in animals. Antipsychotic drug administration augments PPI under certain conditions. Comparisons between normal and neurotensin-deficient mice revealed striking differences in the ability of different antipsychotic drugs to augment PPI. While the atypical antipsychotic drug clozapine augmented PPI normally in neurotensin-deficient mice, the conventional antipsychotic haloperidol and the newer atypical antipsychotic quetiapine were ineffective in these mice, in contrast to normal mice where these drugs significantly augmented PPI. These results suggest that certain antipsychotic drugs require neurotensin for at least some of their effects. Neurotensin-deficient mice also display defects in striatal activation following haloperidol, but not clozapine administration in comparison to normal wild type mice, indicating that striatal neurotensin is required for the full spectrum of neuronal responses to a subset of antipsychotic drugs.
Neurotensin is an endogenous neuropeptide involved in thermoregulation that can induce hypothermia and neuroprotection in experimental models of cerebral ischemia.
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