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Immunomodulation by tachykinin neuropeptides
J P McGillis1, M Mitsuhashi, D G Payan
1Howard Hughes Medical Institute, University of California 94143.
Annals of the New York Academy of Sciences
|January 1, 1990
Summary
Substance P (SP), a neuropeptide, modulates immune and inflammatory responses by binding to specific receptors on lymphocytes and macrophages. This interaction influences cellular functions and may play a role in diseases like rheumatoid arthritis.
Area of Science:
- Neuroimmunology
- Neuropeptide signaling
Background:
- Substance P (SP) is an 11-amino-acid neuropeptide synthesized in peripheral nervous system sensory neurons.
- SP functions as a neurotransmitter and significantly influences immune and inflammatory processes.
- It impacts the proliferation and physiological functions of lymphocytes and macrophages.
Purpose of the Study:
- To elucidate the role of Substance P in immune and inflammatory responses.
- To characterize the Substance P receptor on human lymphocytes.
- To identify cellular responses mediated by Substance P binding.
Main Methods:
- Biochemical and kinetic characterization of SP receptors.
- Identification of SP binding proteins on human lymphocyte membranes.
- Analysis of cellular responses following SP receptor activation.
Main Results:
- A 58,000-MW hydrophobic glycoprotein was identified as the primary SP binding protein on human lymphocyte cell membranes.
- Substance P binding triggers various cellular responses, including phosphatidyl inositol turnover, arachidonic acid metabolism, immunoglobulin synthesis, and enzyme production/secretion.
- Evidence suggests SP's role in the pathophysiology of inflammatory diseases like rheumatoid arthritis.
Conclusions:
- Substance P is a key modulator of immune and inflammatory responses through specific high-affinity receptors.
- The identified SP receptor glycoprotein on lymphocytes mediates significant cellular signaling pathways.
- SP's involvement in inflammation suggests therapeutic potential for related diseases.