TACHYKININ RECEPTORS AND RECEPTOR SUBTYPES

The tachykinins, substance P, neurokinin A and neurokinin B, are a fam ily of neuropeptides widely distributed in the mammalian central and p eripheral nervous system. In the peripheral nervous system, tachykinin s released from peripheral endings of sensory nerves are responsible f or the neurogenic inflammation phenomenon. In the spinal cord/central nervous system, tachykinins play a role in pain transmission/perceptio n and in some autonomic reflexes and behaviors. Their actions are medi ated by three distinct receptors, termed NK1, NK2 and NK3. All tachyki nin receptors belong to the superfamily of G protein-coupled receptors , with seven putative transmembrane spanning segments. In the past few years, a number of potent and selective antagonists, of both peptide and nonpeptide nature, has been developed for the NK1, NK2 and NK3 rec eptors. The contemporary isolation and cloning of the three tachykinin receptors enable now to study the molecular determinants for the inte raction of natural tachykinins with their receptors, and the mechanism by which the antagonists interfere in this process. Furthermore, the introduction of tachykinin antagonists has revealed a striking species -related heterogeneity among the tachykinin receptors, and has also su ggested a possible intra-species heterogeneity for both NK1 and NK2 re ceptors. However, molecular biology studies are needed to prove the ex istence of true tachykinin receptor subtypes.