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Serotonin 5‐HT 2A Receptor Activation Inhibits Cytokine‐stimulated Inducible Nitric Oxide Synthase in C6 Glioma Cells a
Author(s) -
MILLER K. J.,
GONZALEZ H. A.
Publication year - 1998
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1998.tb10188.x
Subject(s) - ritanserin , chelerythrine , nitric oxide synthase , nitric oxide , chemistry , cytokine , receptor , pharmacology , serotonergic , serotonin , signal transduction , protein kinase c , biology , immunology , biochemistry , organic chemistry
C6‐glioma cells endogenously express both 5‐HT 2A receptors and inducible nitric oxide synthase (iNOS). iNOS can be induced by transcriptional activation to produce nitric oxide (NO) in response to a challenge with the pro‐inflammatory cytokines TNF‐α and IFN‐γ. Experiments were conducted to determine whether 5‐HT 2A receptor activation could modify the production of NO in response to the inducing agents. 1 μM DOI produced a dose‐dependent inhibition of the cytokine‐inducted nitrite levels of 40% which was inhibited by spiperone and ritanserin. In addition, the DOI‐mediated decrease was prevented by the PKC inhibitor chelerythrine (100 nM). The effectiveness of DOI was lost when added more than two hours after the addition of inducing agent, suggesting that DOI was regulating iNOS at the level of transcription rather than post‐translationally. We suggest that there is a link between the serotonergic system and NO‐mediated immune responses in the brain.