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Molecular Mechanism of Substance P Mediated Signaling in Lymphatic System
Author(s) -
Chakraborty Sanjukta,
Zawieja David C,
Muthuchamy Mariappan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.764.6
Subject(s) - lymphatic system , microbiology and biotechnology , phosphorylation , substance p , mapk/erk pathway , chemistry , receptor , biology , signal transduction , neuropeptide , immunology , biochemistry
The lymphatic system plays a key role in body fluid homeostasis, lipid absorption and immunity, and these vital functions rely on the contractile activity of the lymphatic muscle cells. However the molecular mechanisms governing lymphatic contractility is not completely understood. We have previously shown that substance P (SP), a neuropeptide associated with the sensory innervation of lymphoid tissue, modulates lymphatic vessel function and lymph flow. In this study we tested the hypothesis that SP increases the myosin light chain 20 (MLC 20 ) phosphorylation and modulates lymphatic contractile dynamics. Lymphatic muscle cells (LMCs) were subjected to various agonists of which SP had the most potent effect on MLC 20 phosphorylation. SP mediates its various biological responses through the G protein coupled neurokinin (NK) receptors, NK1R, NK2R and NK3R. However, it is unknown which specific receptors or pathways are activated by SP action on the lymphatics. Molecular analyses demonstrate the expression of both NK1R and NK3R in LMCs and lymphatic tissues. Immunofluorescence data show the presence of NK1R in the cytoplasm, whereas, NK3R is predominantly present in the nuclei. Furthermore SP treatment is found to activate the p38 MAPK pathway. We propose that SP modulates lymphatic contractility by regulating MLC 20 phosphorylation via p38 MAPK pathway. NIH Support RO1 HL080526 , KO2 HL086650 to MM; HL75199 to DCZ.