Tachykinins

More than 70 years have elapsed since U. S. von Euler and I. H. Gaddum dis covered an unidentified depressor substance in the brain and gut. The effects of the powdery extracts were marked as 'P' on the kymograph tracings, and the nondescript name of 'substance P' still carries the breath of this adventurous period. In the 1960s, substance P returned in another disguise, staging as a hypothalamic peptide that causes copious salivary secretion (see chapter by F. Lembeck and I. Donnerer). This time, though, the mysterious substance was tracked down by S. E. Leeman and her collaborators as an undecapeptide, after it had eluded its identification for some 40 years. Substance P turned out to be the mammalian counterpart of a family of peptides which had been extracted from amphibian and nonvertebrate species and which had been given the name 'tachykinins' by V. Erspamer. Soon novel members of this peptide family were discovered, and in mammals substance P was joined by neurokinin A and neu rokinin B. The presence of tachykinins in frog skin as well as in venoms and toxins of microbes and arachnids raises the possibility that these peptides re present an old system of biological weapons that have been transformed to a particular messenger system in mammals.

History of a Pioneering Neuropeptide: Substance P. - The Tachykinin Peptide Family, with Particular Emphasis on Mammalian Tachykinins and Tachykinin Receptor Agonists. - The Histochemistry of Tachykinin Systems in the Brain. - The Nomenclature of Tachykinin Receptors. - The Mechanism and Function of Agonist-Induced Trafficking of Tachykinin Receptors. - Tachykinin NK1 Receptor Antagonists. - Tachykinin NK2 Receptor Antagonists. - Tachykinin NK3 Receptor Antagonists. - Combined Tachykinin NK1, NK2, and NK3 Receptor Antagonists. - Pre-protachykinin and Tachykinin Receptor Knockout Mice. - Therapeutic Potential of Tachykinin Receptor Antagonists in Depression and Anxiety Disorders. - The Role of Tachykinins and the Tachykinin NK1 Receptor in Nausea and Emesis. - Substance P (NK1 Receptor Antagonists-Analgesics or Not? . - Role of Tachykinins in Neurogenic Inflammation of the Skin and Other External Surfaces. - Role of Tachykinins in Obstructive Airway Disease. - Role of Tachykinins in the Gastrointestinal Tract.