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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022961-05
Application #
3405828
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-12-01
Project End
1993-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Mantyh, P W; Ghilardi, J R; Rogers, S et al. (1993) Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide. J Neurochem 61:1171-4
Maggio, J E; Stimson, E R; Ghilardi, J R et al. (1992) Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. Proc Natl Acad Sci U S A 89:5462-6
Mantyh, P W; Catton, M D; Allen, C J et al. (1992) Receptor binding sites for cholecystokinin, galanin, somatostatin, substance P and vasoactive intestinal polypeptide in sympathetic ganglia. Neuroscience 46:739-54
Mantyh, P W; Catton, M; Maggio, J E et al. (1991) Alterations in receptors for sensory neuropeptides in human inflammatory bowel disease. Adv Exp Med Biol 298:253-83
Too, H P; Maggio, J E (1991) Immunocytochemical localization of neuromedin K (neurokinin B) in rat spinal ganglia and cord. Peptides 12:431-43
Guard, S; Watson, S P; Maggio, J E et al. (1990) Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes. Br J Pharmacol 99:767-73
Mantyh, P W; Catton, M D; Boehmer, C G et al. (1989) Receptors for sensory neuropeptides in human inflammatory diseases: implications for the effector role of sensory neurons. Peptides 10:627-45
Mantyh, P W; Gates, T; Mantyh, C R et al. (1989) Autoradiographic localization and characterization of tachykinin receptor binding sites in the rat brain and peripheral tissues. J Neurosci 9:258-79
Too, H P; Cordova, J L; Maggio, J E (1989) A novel radioimmunoassay for neuromedin K. I. Absence of neuromedin K-like immunoreactivity in guinea pig ileum and urinary bladder. II. Heterogeneity of tachykinins in guinea pig tissues. Regul Pept 26:93-105
Mantyh, P W; Johnson, D J; Boehmer, C G et al. (1989) Substance P receptor binding sites are expressed by glia in vivo after neuronal injury. Proc Natl Acad Sci U S A 86:5193-7

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