Inhibition of serotonin-induced Ca2+ mobilization by interleukin-1 beta in rat C6BU-1 glioma cells.
To study the potential interaction between cytokine and serotonin (5-HT) signal transduction, we evaluated the effect of interleukin-1 beta (IL-1 beta) on the 5-HT2 receptor-mediated mobilization of intracellular Ca2+ in cultured rat C6BU-1 glioma cells. Pretreatment of cells with IL-1 beta significantly inhibited the 5-HT-induced mobilization of Ca2+ in a dose (30-1000 U/ml)- and time (12-24 h)-dependent manner. Inhibition was observed when cells were stimulated with concentrations of 5-HT of > or = 1 microM, which induced the maximal 5-HT response. Lipopolysaccharide (1 microgram/ml) also inhibited 5-HT-induced Ca2+ mobilization, but heat-inactivated IL-1 beta as well as interferon-alpha (1000 U/ml), interferon-gamma (1000 U/ml), and tumor necrosis factor-alpha (2000 U/ml) did not. The inhibitory effects of IL-1 beta and LPS were significantly prevented by genistein, a selective tyrosine kinase antagonist, and by H7, a potent inhibitor of protein kinase C. These results indicate that IL-1 beta and LPS inhibit 5-HT2 receptor-mediated Ca2+ mobilization via pathways that include the activation of a tyrosine kinase and protein kinase C. The interaction between cytokines (IL-1 beta) and monoamines (5-HT) may serve to modulate signal transduction in the central nervous system.
Kugaya
A
A
Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Japan.
Kagaya
A
A
Uchitomi
Y
Y
Motohashi
N
N
Yamawaki
S
S
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein; D005910:Glioma / Q000378:metabolism; D006131:Growth Inhibitors / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D012486:Salmonella typhimurium; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D007375:Interleukin-1; D007529:Isoflavones; D007546:Isoquinolines; D008070:Lipopolysaccharides; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019833:Genistein; D011493:Protein Kinase C; D002118:Calcium