title: Desflurane increased the activity of excitatory amino-acid carrier 1 (EAAC1) expressed in Xenopus oocytes.
abstract: Desflurane is a volatile anaesthetic agent with neuroprotective properties. Excitatory amino-acid carrier 1 (EAAC1) may be neuroprotective by taking up glutamate and cysteine. Therefore, the effects of desflurane on EAAC1 activity were investigated in this study. EAAC1 was expressed in Xenopus laevis oocytes. Two-electrode voltage-clamping technique was used to record membrane currents upon exposure to l-glutamate (30 μM) in the presence or absence of desflurane (0.4, 1.0, 2.0, 2.6, or 3.2mM). Currents were also measured in oocytes pre-exposed to a protein kinase C (PKC) activator (50 nM phorbol-12-myristate-13-acetate, PMA), PKC inhibitors (1 μM staurosporine or 50 μM chelerythrine), or phosphatidylinositol-3-kinase (PI3K) inhibitors (5 μM wortmannin or 10 μM LY294002). Desflurane significantly increased EAAC1 activity. The EC50 of desflurane for increasing the EAAC1 response was 0.75 mM. A kinetic study showed that desflurane significantly increased the Vmax but had no effect on the Km of the EAAC1 response for glutamate. Treatment of oocytes with desflurane plus PMA significantly increased the transporter currents compared to the control, but did not further increase the response compared to either agent alone. Staurosporine attenuated desflurane-enhanced transporter currents without decreasing the basal activity; chelerythrine did not decrease either. In addition, pretreatment of oocytes with two PI3K inhibitors (wortmannin or LY294002) significantly reduced desflurane-enhanced EAAC1 activity without decreasing basal activity. Our results suggest that desflurane increases EAAC1 activity via PKC or PI3K. This enhanced EAAC1 activity may be a mechanism for the neuroprotective effect of desflurane.
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Seongnam-si, South Korea.
authors.forename: Seong-Joo
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Seongnam-si, South Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Shin
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Seongnam-si, South Korea.
authors.forename: Bon-Wook
authors.initials: BW
authors.lastname: Gu
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Kyoung-In
authors.initials: KI
authors.lastname: Woo
authors.affiliation: Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Seongnam-si, South Korea.
authors.forename: Sang-Hwan
authors.initials: SH
authors.lastname: Do
authors.affiliation: Department of Anesthesiology and Pain medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Seongnam-si, South Korea. Electronic address: jinaryu@lycos.co.kr.
authors.forename: Jung-Hee
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D000077335:Desflurane; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D050580:Excitatory Amino Acid Transporter 3 / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009865:Oocytes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014982:Xenopus laevis / Q000235:genetics*
chemical_list: D000777:Anesthetics; D050580:Excitatory Amino Acid Transporter 3; D018696:Neuroprotective Agents; C493398:Slc1a1 protein, rat; D000077335:Desflurane; D007530:Isoflurane; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C
keywords: Desflurane; Glutamate transporters; Phosphatidylinositol-3-kinase; Protein kinase C; Xenopus oocyte