S-Space College of Medicine/School of Medicine (의과대학/대학원) Anesthesiology and Pain Medicine (마취통증의학전공) Journal Papers (저널논문_마취통증의학전공)
Effects of intravenous anesthetics on the activity of glutamate transporter EAAT3 expressed in Xenopus oocytes: evidence for protein kinase C involvement
- Yun, Jung-Yeon; Kim, Jin-Hee; Kim, Hae-Kyoung; Lim, Young-Jin; Do, Sang-Hwan; Zuo, Zhiyi
- Issue Date
- Eur J Pharmacol. 2006 Feb 15;531(1-3):133-9. Epub 2006 Jan 18.
- Alkaloids; Anesthetics, Intravenous/*pharmacology; Animals; Benzophenanthridines; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; Etomidate/pharmacology; Excitatory Amino Acid Transporter 3/genetics/*physiology; Female; Glutamic Acid/pharmacology; Ketamine/pharmacology; Membrane Potentials/drug effects; Oocytes/*drug effects/metabolism/physiology; Phenanthridines/pharmacology; Protein Kinase C/antagonists & inhibitors/metabolism; Rats; Staurosporine/pharmacology; Tetradecanoylphorbol Acetate/pharmacology; Thiopental/pharmacology; Xenopus
- We investigated the effects of the intravenous anesthetics, thiopental, etomidate and ketamine, on the activity of one type of glutamate transporters, EAAT3 (excitatory amino acid transporter type 3). Rat EAAT3 was expressed in Xenopus oocytes by injection of its mRNA. Using two-electrode voltage clamp, membrane currents were recorded after the application of L-glutamate (30 microM) in the presence or absence of various concentrations of the anesthetics. Thiopental (0.3-30 microM) and ketamine (3-1000 microM) did not affect EAAT3 activity. Etomidate decreased EAAT3 activity in a concentration-dependent manner (0.10-10 microM). Etomidate at 1 microM significantly decreased the Vmax, but not the Km of EAAT3 for glutamate. Chelerythrine, a protein kinase C (PKC) inhibitor, significantly decreased EAAT3 activity, however, there were no statistical differences among the chelerythrine, etomidate or chelerythrine plus etomidate groups. Likewise, the combination of staurosporine, another PKC inhibitor, and etomidate did not decrease the responses further compared with staurosporine or etomidate alone. Phorbol-12-myrisate-13-acetate, a PKC activator, abolished etomidate-induced decrease in EAAT3 activity. Since our results showed that thiopental and ketamine did not affect EAAT3 activity significantly, EAAT3 may not be a target for their anesthetic effects. Our results also suggest that etomidate, possibly via PKC, decreased EAAT3 activity at clinically relevant concentrations.
- 0014-2999 (Print)
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