The diverse actions of volatile and gaseous anesthetics on human-cloned 5-hydroxytryptamine3 receptors expressed in Xenopus oocytes.
BACKGROUND
General anesthetics can modulate the 5-hydroxytryptamine type 3 (5-HT3) receptor, which may be involved in processes mediating nausea and vomiting, and peripheral nociception. The effects of the new volatile anesthetic sevoflurane and the gaseous anesthetics nitrous oxide (N2O) and xenon (Xe) on the 5-HT3 receptor have not been well-characterized.


METHODS
Homomeric human-cloned 5-HT3A receptors were expressed in Xenopus oocytes. The effects of halothane, isoflurane, sevoflurane, N2O, and Xe on 5-HT-induced currents were studied using a two-electrode, voltage clamping technique.


RESULTS
Halothane (1%) and isoflurane (1%) potentiated 1 mum 5-HT-induced currents to 182 +/- 12 and 117 +/- 2%, respectively. In contrast, sevoflurane (1%), N2O (70%), and Xe (70%) inhibited 5-HT-induced currents to 76 +/- 1, 77 +/- 4, and 34 +/- 4%, respectively. The inhibitory effects were noncompetitive for sevoflurane and competitive for N2O and Xe. None of these inhibitory effects showed voltage dependency.


CONCLUSIONS
Inhalational general anesthetics produce diverse effects on the 5-HT3 receptor. Both halothane and isoflurane enhanced 5-HT3 receptor function in a concentration-dependent manner, which is consistent with previous studies. Sevoflurane inhibited the 5-HT3 receptor noncompetitively, whereas N2O and Xe inhibited the 5-HT3 receptor competitively, suggesting the inhibitory mechanism of sevoflurane might be different from those of N2O and Xe.
Suzuki
Takahiro
T
Department of Anesthesiology, Osaka University Medical School, Osaka, Japan.
Koyama
Hideki
H
Sugimoto
Masahiro
M
Uchida
Ichiro
I
Mashimo
Takashi
T
D000465:Algorithms; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D006221:Halothane / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007530:Isoflurane / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology; D009609:Nitrous Oxide / Q000494:pharmacology; D009865:Oocytes / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077149:Sevoflurane; D014978:Xenon / Q000494:pharmacology; D014982:Xenopus laevis
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000077149:Sevoflurane; D014978:Xenon; D007530:Isoflurane; D009609:Nitrous Oxide; D006221:Halothane