The bioactive peptide substance P is an important mediator in many systems, and research on this neuropeptide is a very active field in the life sciences. Among the reasons for the great interest in substance P are its apparent roles in primary afferent transmission and nociception, the gastrointestinal tract and other smooth muscle systems, inflammation, and the striatonigral pathway. Implicit in nearly all research on substance P until very recently was the assumption that substance P was the only member of the tachykinin family of peptides found in mammals. With the discovery in 1983 that other tachykinins are also present in mammals came the recognition that many of the tools used in past substance P research (e.g. antisera, antagonists, radioligands) lacked the specificity to discriminate between the mammalian tachykinins and their receptors. The goal of the proposed studies is to further develop and apply tools for tachykinin research which do have the specificity to discriminate between the various members of the tachykinin family. Using novel specific antisera for radioimmunoassay and immunocytochemistry (specific aim 1) and novel specific radioligands for receptor studies (specific aim 2), we will be able to extend tachykinin research to include all members of the tachykinin family. While we will be concentrating our efforts on particular tachykinin systems relevant to primary afferent transmission and inflammation, the major significance of the proposed studies is the application of the above specific tools and techniques, which will be essential to future research in a variety of systems where tachykinins play an important role.
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