The bioactive peptide substance P is an important mediator of a wide variety of functions in a wide variety of systems. Althoug substance P belongs to a family of peptides (the tachykinins), it was believed until recently to be the only member of that family in mammals. Implicit in most of the research on substance P was the assumption that no other tachykinins exist in mammals. In 1983, we reported that mammalian tissues contain not only substance P, but also substance K and neuromedin K. We have gone on to show that the three tachykinins have different tissue distributions and different receptors. The discovery of the new tachykinins has cast much of previous substance P research in some doubt, because the great structural similarity of these three peptides probably means that many of the biological functions now thought to be mediated by substance P may in fact be mediated by one of the new peptides. The tools used in substance P research up to now (e.g. the antagonists used in pharmacological studies and the antisera used in immunohistochemical studies) lack the specificity to descriminate between the three mammalian tachykinins. The goal is to further develop and apply techniques for tachykinin research that do have the specificity to discriminate between the various members of the peptide family. Using novel specific antisera for immunocytochemistry (specific aim 1) and novel specific radioligands for receptor studies (specific aim 2), we will be able to confirm (or correct) some current theories about substance P and extent tachykinin research to include all members of the peptide family. Only by the application of such techniques can the vast efforts already invested in substance P research over the last half-century be fully exploited. The significance of the proposed studies is the development of those specific tools and techniques, which will be crucial to research in a wide variety of systems (inflammation, nociception, smooth muscle, etc.) in which tachykinins play an important role.

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National Institute of Neurological Disorders and Stroke (NINDS)
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Neurological Sciences Subcommittee 1 (NLS)
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Harvard University
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