ID 282
Title Transcription
アフリカ ツメガエル ランボ サイボウ ニ ハツゲン シタ セロトニン トランスポーター ニ タイスル マスイヤク ノ サヨウ
Title Alternative
The Effects of Anesthetics on Serotonin Transporter Expressed in Xenopus Oocytes
Author
Kaneko, Miyuki Department of Dental Anesthesiology, Graduate School of Dentistry, The University of Tokushima
Keywords
セロトニントランスポーター
麻酔薬
アフリカツメガエル卵母細胞
プロテインキナーゼC
Content Type
Departmental Bulletin Paper
Description
Serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT) is the only functional membrane protein responsible for efficient synaptic clearance of extracellular 5-HT which has psychotogenic properties. Anesthetics clinically contribute to psychosedation to relieve phobia or anxiety accompanied with dental treatment. Nevertheless, little is known about the effects of anesthetics on SERT. In this study, [^3H]5-HT uptake assay and two-electrode voltage-clamp method were utilized to examine directly the effects of anesthetics on the human SERT expressed in Xenopus oocytes. Ketamine (1-100μM) significantly inhibited SERT function in concentration- and voltage dependent manners (IC_<50>=4μM). Eadie-Hofstee analysis showed a significant increase in Km (control ; 2.37±0.83μM, 10μM of ketamine ; 12.11±4.69μM) with no significant changes in the apparent Vmax (control ; 12.60±1.14pmol/oocyte/hr, 10μM of ketamine ; 14.67±2.66pmol/oocyte/hr), suggesting that ketamine competitively inhibited [^3H]5-HT uptake. Propofol inhibited [^3H]5-HT uptake and 5-HT-induced inward current only at high concentration (100μM). Pentobarbital (5-500μM) did not have significant effect on SERT function. Neither sevoflurane (50μM-2mM) nor isoflurane (50μM-2mM) had significant effect to SERT functiton. Interestingly, lidocaine (10nM-1μM) inhibited [^3H]5-HT uptake in a dose-dependent manner and [^3H]5-HT uptake was completely inhibited by 1μM of lidocaine. Eadie-Hofstee analysis showed a significant decrease in Vmax (control ; 13.28±2.07μM, 500nM of lidocaine ; 9.33±1.14μM) with no significant changes in Km (control ; 15.98±6.26pmol/oocyte/hr, 500nM of Lidocaine ; 15.81±4.91pmol/oocyte/hr), suggesting that lidocaine non-competitively inhibited [^3H]5-HT uptake. Intracellular QX314 (permanently charged lidocaine analogue) inhibited the [^3H]5-HT uptake by SERT, but intracellular or extracellular benzocaine (permanently uncharged local anesthetics) was without effect. These results suggest that the action sites of lidocaine on SERT seem to be located intracellularly. The effect of lidocaine was partially abolished in the present of staurosporine, protein kinase C inhibitor. In conclusion, these results suggest that ketamine and lidocaine directly inhibit SERT function at clinical concentrations, and PKC may partially be responsible for lidocaine-induced inhibition of SERT function.
Journal Title
四国歯学会雑誌
ISSN
09146091
NCID
AN10050046
Volume
19
Issue
1
Start Page
117
End Page
129
Sort Key
117
Published Date
2006-06
Remark
公開日:2010年1月24日で登録したコンテンツは、国立情報学研究所において電子化したものです。
FullText File
language
jpn
Report Type
学位論文