Substance P: a pioneer amongst neuropeptides

A brief overview of recent developments in the substance P field is provided, in addition to a historical introduction. It is emphasized that there are multiple tachykinins and tachykinin receptors and that there are examples of coexistence of several tachykinin peptides and of several tachykinin receptors in single cells, and there is evidence for tachykininergic cotransmission. The distribution and functional significance of tachykinins in the gastrointestinal tract and in sensory neurones, and interactions with other peptides and transmitters, are reviewed. The recent production of knock-out mice for either substance P or the NK1 receptor is discussed, as well as the exciting concept of substance P receptor internalization. Finally, the development of specific substance P antagonists is summarized, and possible clinical implications discussed, and, in particular, a recent study which reports that a substance P antagonist shows clinical efficacy in depression.