Neurotensin

GI / Neuromodulation

Also known as: NT, Neurotensin-13, NTS

Neurotensin FamilyResearch phase: Endogenous peptide (well characterized)Regulatory: Endogenous peptide. Pro-neurotensin is used as a metabolic biomarker. Neurotensin analogs have been explored for schizophrenia and pain.

Mechanism

Neurotensin is a 13-amino-acid peptide with dual roles in the gut and brain. In the GI tract, it is released from N cells after fat-rich meals and promotes fat absorption, stimulates pancreatic secretion, and modulates gut motility. In the brain, it acts as a neuromodulator, interacting with dopamine systems and producing effects on pain modulation and body temperature regulation.

Technical detail

Neurotensin (pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) signals through NTS1R (Gq-coupled, high affinity) and NTS2R (modulatory, involved in analgesia), both GPCRs, plus NTS3R/sortilin (a sorting receptor). GI effects: released from intestinal N cells by lipids, stimulates pancreatic enzyme/bicarbonate secretion, intestinal motility, and mesenteric blood flow. CNS effects: NTS1R activation in VTA modulates dopaminergic neurotransmission (neurotensin is an "endogenous neuroleptic"), produces hypothermia and non-opioid analgesia. Pro-neurotensin fragment (pro-NT) is a biomarker for cardiometabolic risk.

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