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.
The influence of local and general anaesthetics on cation influx through the fast, voltage-dependent sodium channel and the 5-HT3 receptor cation channel was studied in N1E-115 mouse neuroblastoma cells by measuring 2-min influx of the organic cation 14C-guanidinium induced by either veratridine (1 mmol/l) or 5-HT (100 mumol/l). The veratridine-induced influx of 14C-guanidinium was potentiated by scorpion toxin and inhibited by tetrodotoxin. The 5-HT-induced 14C-guanidinium influx was not affected by tetrodotoxin but it was inhibited by nanomolar concentrations of the selective 5-HT3 receptor antagonists ondansetron and ICS 205-930; at high micromolar concentrations these compounds also inhibited the veratridine-induced influx of 14C-guanidinium. The 14C-guanidinium influx through both channels was inhibited by local and general anaesthetics. The rank order of potency for inhibition of veratridine-induced influx by local anaesthetics was tetracaine > bupivacaine > cocaine > lidocaine > procaine and that for inhibition of the 5-HT3 receptor channel was tetracaine > bupivacaine > cocaine > procaine > lidocaine. With the exception of procaine and cocaine, which were equipotent at both channels, the local anaesthetics were 4.4-fold (lidocaine) to 25-fold (tetracaine) more potent at the fast sodium channel than at the 5-HT3 receptor channel. The rank order of potency for general anaesthetics was propofol > etomidate = alfaxalone = ketamine > thiopental = methohexital at the fast sodium channel, and propofol > or = etomidate > alfaxalone = methohexital > thiopental > ketamine at the 5-HT3 receptor channel.(ABSTRACT TRUNCATED AT 250 WORDS)
Barann
M
M
Institut für Pharmakologie und Toxikologie, Universität Bonn, Federal Republic of Germany.
Göthert
M
M
Fink
K
K
Bönisch
H
H
D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D019791:Guanidine; D006146:Guanidines / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism / Q000648:ultrastructure*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014701:Veratridine / Q000494:pharmacology
D000777:Anesthetics; D000779:Anesthetics, Local; D002250:Carbon Radioisotopes; D006146:Guanidines; D007473:Ion Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D015222:Sodium Channels; D012701:Serotonin; D014701:Veratridine; D019791:Guanidine