Comparison of fast responses to serotonin and 2-methyl-serotonin in voltage-clamped N1E-115 neuroblastoma cells.
The activation of 5-HT3 receptors by 5-HT and 2-methyl-5-HT was studied with 'concentration-jump' techniques in voltage-clamped N1E-115 cells grown in culture. When applied to single cells with a fast perfusion technique, both agonists induced currents the on-rate kinetics of which were concentration-dependent. Based on the time constants of current kinetics and subsequent estimates of agonist association and dissociation rates, an apparent Kd of 1.3 microM was determined for 5-HT, a value in agreement with binding and functional studies. Receptor activation by 2-methyl-5-HT was slower, consistent with its lower potency as compared to the parent compound. In addition, the rise time of 2-methyl-5-HT-mediated currents was affected by hyperpolarizing membrane potential. The results show evidence of different molecular behaviors for the two agonists.
Mienville
J M
JM
SANOFI Recherche, Montpellier, France.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004594:Electrophysiology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D012701:Serotonin; C045918:2-methyl-5-HT