Characterization of the cellular and molecular determinants for the internalization of the high affinity neurotensin receptor

Neurotensin is a thirteen amino acid peptide that is found both in the central and peripheral nervous systems. In the CNS, it controls the synthesis and release of dopamine, modulates anterior pituitary hormone secretion, and provides non-opioid-receptor-dependent analgesia. In the gut, it modulates gastric acid secretion, pancreatic secretion, and colonic motility. In the immune system, it modulates IL-1 and mast cell secretion and stimulates macrophage phagocytosis. Neurotensin also acts as a growth factor for normal and cancer cells. Neurotensin mediates its effects through three neurotensin receptors: NTR1, NTR2, and NTR3. NTR1 and NTR2 belong to the G-protein coupled receptor (GPCR) family, while NTR3 is a single transmembrane receptor identical to sortilin. NTR1 has the highest affinity for neurotensin (Kd of 0.1--0.3 nM). Internalization of GPCRs, including NTR1 and NTR2, was shown to play an important role in initiating signaling activity as well as in desensitizing and resensitizing the receptors.In this study, the internalization of the NTR1 was investigated. (Abstract shortened by UMI.