Inhibition by anaesthetics of 14C-guanidinium flux through the voltage-gated sodium channel and the cation channel of the 5-HT3 receptor of N1E-115 neuroblastoma cells.

摘要: Effects of some naturally occurring steroids and synthetic analogues on the cation flux through channel 5-HT3 receptor voltage-gated tetrodotoxin-sensitive sodium were studied in N1E-115 mouse neuroblastoma cells by measuring 2-min influx organic [14C]-guanidinium. The fluxes intact either induced 2 min exposure to 5-hydroxytryptamine (5-HT, 100microM) or veratridine (1 mM). Influx [14C]-guanidinium both channels was concentration-dependently inhibited all compounds studied. rank order potency for inhibition receptor-induced clomiphene approximately/= cyproterone acetate > estradiol progesterone allotetrahydrodeoxycorticosterone alfaxalone testosterone aldosterone dexamethasone. With exception dexamethasone testosterone, which more potent at voltage-dependent channel, about nearly equipotent inhibiting channels, twofold (alfaxalone, allotetrahydrodeoxycorticosterone) 107-fold (cyproterone acetate) than channel. potencies (and analogues) correlated with their lipophilicity (log P values). A similar correlation between log values pIC50 steroid-induced veratridine-evoked only found when (a compound extremely low inhibitory this channel) not included regression analysis. results indicate that are targets steroids. relationship most is compatible a common mechanistic principle two i.e. nonspecific hydrophobic interaction certain membrane lipids neighbourhood channels.