5-HT3 receptor-channels coupled with Na+ influx in human T cells: role in T cell activation.
The study was conducted on a human (Jurkat) T cell line, loaded with a Na+ fluorescent probe, SBFI/AM. Serotonin and an agonist of 5-HT3 receptor-channels, 2-methyl-5HT, evoked Na+ influx, whereas the agonists of other serotonergic receptor subtypes, i.e., 5-HT1A and 5-HT1B receptors, failed to induce Na+ influx in these cells. By using 3H-BRL43694, an agonist of 5-HT3 receptor-channels, we characterized 5-HT3 lymphocyte receptors which exhibited a density (Bmax) of 300 +/- 20 fmol/10(6) cells and a Kd of 30 nM in Jurkat T cells. The T-cell 5-HT3 receptor-channel is not regulated either by the protein kinase C or by the free intracellular calcium concentrations as the agents known to activate the PKC and to induce increases in intracellular free calcium concentrations failed to influence the free intracellular Na+ concentrations, [Na+]i, in these cells. Furthermore, an increase in [Na+]i, induced by 2-methyl-5HT, via 5-HT3 receptor-channels seems to stimulate T-cell activation by facilitating the progression of T cells from S to G2/M phase of the cell cycle.
Khan
N A
NA
Laboratoire de Nutrition Cellulaire et Métabolique, Université de Bourgogne, Dijon, France. naim.khan@u-bourgogne.fr
Poisson
J P
JP
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004789:Enzyme Activation; D017829:Granisetron / Q000494:pharmacology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D019169:Jurkat Cells / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology*; D008787:Metoclopramide / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology; D010835:Phytohemagglutinins / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012433:Ryanodine / Q000494:pharmacology; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D017829:Granisetron; D008787:Metoclopramide; D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D010879:Piperazines; D011493:Protein Kinase C; D011810:Quinoxalines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012433:Ryanodine; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012964:Sodium; D015222:Sodium Channels; D019284:Thapsigargin; C470302:HTR1B protein, human; C052561:CGS 12066B; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C045918:2-methyl-5-HT