Ionotrophic 5-hydroxytryptamine type 3 receptor activates the protein kinase C-dependent phospholipase D pathway in human T-cells.
The present study was undertaken to investigate the role of the 5-hydroxytryptamine (5-HT) ionotrophic receptor 5-HT(3) in the activation of human Jurkat T-cells. 5-HT and 2-methyl-5-HT (2Me-5-HT), an agonist of the 5-HT(3) receptor, induced increases in intracellular free Na(+) concentrations, [Na(+)](i), via opening of the ionotrophic receptor in these cells. These two serotonergic (5-hydroxytryptaminergic) agents potentiated phytohaemagglutinin (PHA)-induced T-cell activation. However, they failed to potentiate dioctanoglycerol-plus-ionomycin-stimulated T-cell blastogenesis. Interestingly, an inhibitor of protein kinase C (PKC), GF 109203X, curtailed significantly 5-HT and 2Me-5-HT-potentiated T-cell activation. These results demonstrate that the opening of the 5-HT(3) ionotrophic receptor is implicated in T-cell activation via the PKC pathway. Furthermore, 5-HT and 2Me-5-HT stimulated phospholipase D (PLD) activity, as measured by the production of phosphatidylethanol and phosphatidylbutanol at the expense of phosphatidic acid (PA). GF 109203X significantly curtailed the 5-HT- and 2Me-5-HT-induced PLD activity and T-cell activation. The PLD/PA pathway stimulated by these two serotonergic agents resulted in the production of 1,2-diacylglycerol (DAG) mass in Jurkat T-cells. These results altogether suggest that 5-HT and 2Me-5-HT potentiate T-cell activation via increases in [Na(+)](i) and the activation of the PKC-dependent PLD pathway.
Khan
N A
NA
UPRES Lipides et Nutrition, Université de Bourgogne, Faculté des Sciences-Mirande, 9 avenue Alain Savary, 21011 Dijon Cedex, France. Naim.Khan@u-bourgogne.fr
Hichami
A
A
D002453:Cell Cycle; D004075:Diglycerides / Q000096:biosynthesis / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D008301:Maleimides / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
D004075:Diglycerides; D004791:Enzyme Inhibitors; D007211:Indoles; D007476:Ionophores; D008301:Maleimides; D010835:Phytohemagglutinins; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; C044295:1,2-dioctanoylglycerol; D012701:Serotonin; D015759:Ionomycin; C045918:2-methyl-5-HT; D012964:Sodium; D011493:Protein Kinase C; D010739:Phospholipase D; C070515:bisindolylmaleimide I