UCSD Molecule Pages

Neurokinin-1 receptor (NK1R), or substance P receptor, is a G protein-coupled receptor (GPCR) that transmits the signal of substance P (SP) and other tachykinins. Upon stimulation by its agonist SP, NK1R has been shown to interact with multiple G proteins, including Gs, Gq/11, Gi/o, G12, and G13. NK1R undergoes a rapid agonist-dependent desensitization, which is mediated by members of G protein receptor kinases (GRKs) and β-arrestins. NK1R is widely distributed in the central and peripheral nervous systems, as well as in the gastrointestinal tract, immune system, and skin. NK1R plays a key role in many physiological and pathophysiological processes, including pain, inflammation, cancer, brain edema, traumatic brain injury, nausea and vomiting, affective disorders, and obesity. Several pharmaceutical companies are actively developing compounds to target NK1R for its therapeutic potential. The first FDA approval for a NK1R antagonist was obtained in 2003 for aprepitant, which is indicated for chemotherapy-induced nausea and vomiting.