Modulation of serotonin-induced currents by metals in mouse neuroblastoma cells.
The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch clamp technique was used to record currents induced by serotonin at a concentration of 3 microM which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 microM and 2 microM, respectively. Lead and zinc suppressed the current with IC50S of 80 microM and 50 microM, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 microM, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 microM, and the effect was reversible. Aluminum at 100 microM, had no effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.
Uki
M
M
Otsuka Pharmaceutical Company, Japan.
Narahashi
T
T
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D007473:Ion Channels / Q000187:drug effects*; D008670:Metals / Q000633:toxicity*; D051379:Mice; D009447:Neuroblastoma; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D007473:Ion Channels; D008670:Metals; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists