Neurotensin receptor 1

Neurotensin receptor type 1 (NTSR1) is a member of the class A G protein-coupled receptor (GPCR) superfamily, characterized by its canonical structure of seven transmembrane α-helices connected by extracellular and intracellular loops.^[8] High-resolution crystal structures of NTSR1 have been determined in various functional states, including complexes with peptide agonists (such as the endogenous neurotensin fragment NTS8-13), non-peptide agonists, partial agonists, and antagonists, as well as in the ligand-free (apo) state.^[9][10]

The neurotensin binding pocket is located on the extracellular side of the receptor, where neurotensin binds in an extended conformation nearly perpendicular to the membrane, with the C-terminus oriented toward the receptor core.^[10] Key interactions involve charged residues in the binding pocket and the C-terminal arginine of neurotensin, while the receptor's activation is associated with conformational changes that propagate from the ligand-binding site through the transmembrane helices to the intracellular side.^[9] The intracellular region of NTSR1 interacts with G proteins and β-arrestins, facilitating downstream signaling and receptor internalization; phosphorylation of specific intracellular sites is critical for stable β-arrestin binding.^[11] Notably, the receptor also contains an amphipathic helix 8 following transmembrane helix 7, although its stability and presence may vary among different receptor states and constructs.^[12]

Neurotensin receptor 1, also called NTSR1, belongs to the large superfamily of G-protein coupled receptors and is considered a class A GPCR. NTSR1 mediates multiple biological processes through modulation by neurotensin, such as low blood pressure, high blood sugar, low body temperature, antinociception, anti-neuronal damage ^[13] and regulation of intestinal motility and secretion.^[6]

• Neurotensin (NT)
• ML314 – β-arrestin biased modulator^[16]
• SBI-553 - β-arrestin biased modulator^[17]

• Neurotensin receptor