Molecular and cellular regulation of neurotensin receptor under acute and chronic agonist stimulation

Neurotensin is a tridecapteptide acting mostly in the brain and gastrointestinal tract. NT binds two G protein coupled receptors (GPCR), NTS1 and NTS2, and a single transmembrane domain receptor, NTS3/gp95/sortilin receptor. NTS1 mediates the majority of NT action in neurons and the periphery. Like many other GPCRs, upon agonist stimulation, NTS1 is internalized, endocytosed, and the cells are desensitized. It is tacitly acknowledged that the intensity and the lasting of cellular responses to NT are dependent on free and functional NTS1 at the cell surface. Understanding how NTS1 expression is regulated at the membrane should provide a better comprehension towards its function. This review analyzes and discusses the current cellular and molecular mechanisms affecting the expression of NTS1 at the cellular membrane upon acute and chronic NT stimulation.