Tachykinin/Substance P/Neurokinin-1 Receptors
Tachykinins are small peptides, found in both vertebrates and invertebrates, which regulate many physiological processes. They are distributed mainly in the central nervous system, but are also important regulators of contractility in vascular smooth muscle and many areas of the gastrointestinal tract. Tachykinins (meaning fast acting) are characterized by an amidated C-terminus containing the amino acids F-X-G-L-M-NH2, where X is a hydrophobic amino acid residue. Tachykinins act through receptors that are members of the G-protein-coupled receptor superfamily. The best-known mammalian tachykinin is substance P (SP), a peptide of 11 amino acids. The preferred receptor for SP, neurokinin-1 receptor (NK1R; also known as substance P receptor), occurs as a full-length receptor and in a truncated form, which lacks the carboxyl-tail. The carboxyl tail of NK1R plays an important role in receptor desensitization; therefore, the truncated form of NK1R differs from full-length NK1R in its interactions with proteins involved in receptor desensitization. Finally, NK1R has an important role in pain and in several human disorders, including emesis, depression, and glioblastoma.
