Neurotensin

Neurotensin is a 13-amino-acid neuropeptide that acts as a neurotransmitter and neurohormone in the central nervous system and the gut. It was first isolated from brain tissue in 1973, and its name reflects its abundant neural localization. In tissues, neurotensin is produced as part of a larger precursor, prepro-neurotensin, which is processed to yield the mature peptide.

Biochemically, neurotensin's activity is mediated by three recognized receptors. NTS1 (NTR1) and NTS2 (NTR2) are G protein-coupled receptors with high affinity for neurotensin and distinct signaling profiles. NTS3, also known as sortilin, is a single-pass transmembrane protein that binds neurotensin and participates in trafficking and endocytosis, contributing to intracellular signaling in some contexts. The receptor distribution and signaling pathways underlie the peptide’s diverse effects.

In the brain, neurotensin modulates dopaminergic transmission in reward and motor circuits and influences pain perception, thermoregulation, feeding behavior, and mood. In the gastrointestinal tract, enteroendocrine cells release neurotensin in response to fat intake, where it can stimulate intestinal motility, pancreatic secretion, and fluid absorption, contributing to gut function and nutrient processing. Neurotensin can also interact with other neuropeptide systems and affect autonomic regulation.

Clinical and research relevance includes investigation of neurotensin signaling in psychiatric disorders and cancer. Altered neurotensin activity has been studied in schizophrenia, with findings remaining inconclusive. Receptors, particularly NTR1, are of interest in several cancers, where overexpression can promote tumor growth, prompting exploration of NTR-targeted therapies and antagonists as potential treatments.