Neurotensin

Neurotensin is a 13 is_associated_with::amino acid is_associated_with::neuropeptide that is implicated in the regulation of is_associated_with::luteinizing hormone and is_associated_with::prolactin release and has significant interaction with the is_associated_with::dopaminergic system. Neurotensin was first isolated from extracts of bovine is_associated_with::hypothalamus based on its ability to cause a visible is_associated_with::vasodilation in the exposed cutaneous regions of anesthetized rats.

Neurotensin is distributed throughout the central nervous system, with highest levels in the is_associated_with::hypothalamus, is_associated_with::amygdala and is_associated_with::nucleus accumbens. It induces a variety of effects, including: analgesia, hypothermia and increased locomotor activity. It is also involved in is_associated_with::regulation of dopamine pathways. In the periphery, neurotensin is found in is_associated_with::endocrine cells of the small intestine, where it leads to is_associated_with::secretion and is_associated_with::smooth muscle contraction.

Sequence and biosynthesis
Neurotensin shares significant sequence similarity in its 6 is_associated_with::C-terminal is_associated_with::amino acid residues with several other neuropeptides, including is_associated_with::neuromedin N (which is derived from the same precursor). This C-terminal region is responsible for the full biological activity, the is_associated_with::N-terminal portion having a modulatory role. The neurotensin/neuromedin N precursor can also be processed to produce large 125-138 amino acid is_associated_with::peptides with the neurotensin or neuromedin N sequence at their C-terminus. These large peptides appear to be less potent than their smaller counterparts, but are also less sensitive to degradation and may represent endogenous, long-lasting activators in a number of pathophysiological situations.

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 169-170 amino acid precursor protein that also contains the related neuropeptide is_associated_with::neuromedin N. The peptide coding domains are located in tandem near the is_associated_with::carboxyl terminal end of the precursor and are bounded and separated by paired basic is_associated_with::amino acid (lysine-arginine) processing sites.

Clinical significance
Neurotensin is a potent is_associated_with::mitogen for is_associated_with::colorectal cancer.

Neurotensin has been implicated in the modulation of is_associated_with::dopamine signaling, and produces a spectrum of pharmacological effects resembling those of is_associated_with::antipsychotic drugs, leading to the suggestion that neurotensin may be an endogenous is_associated_with::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 is_associated_with::prepulse inhibition (PPI) of the is_associated_with::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 is_associated_with::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 is_associated_with::thermoregulation that can induce is_associated_with::hypothermia and is_associated_with::neuroprotection in experimental models of is_associated_with::cerebral ischemia.