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Anesthetic Pharmacology
Anesthesia and Pain Medicine 2008;3(4):264-269.
Published online October 30, 2008.
Remifentanil increases the activity of the glutamate transporter, EAAC1, expressed in Xenopus oocytes
Junghee Ryu, Sang Hwan Do, Nanju Lee
1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
2Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
Remifentanil has gained wide clinical acceptance during anesthesia due to its short context-sensitive half time and organ-independent metabolism. However, its mechanism as an anesthetic remains unclear. Glutamate transporters may be important targets for anesthetic action in the central nervous system, and we tested whether remifentanil affected the activity of the primary neuronal glutamate transporter, EAAC1 (excitatory amino acid carrier 1). METHODS: EAAC1 was expressed in Xenopus oocytes by mRNA injection. By using two-electrode voltage clamping, membrane currents were recorded before, during, and after application of L-glutamate (30microM) in the presence or absence of remifentanil. Oocytes were exposed to a protein kinase C (PKC) activator and inhibitor to study the role of PKC on EAAC1 activity. RESULTS: L-Glutamate induced an inward current in EAAC1-expressing oocytes. This response increased in a bell-shaped manner in the presence of 0.1microM to 1 mM remifentanil. Remifentanil significantly increased Vmax (3.1 +/- 0.2microC for controls vs. 4.9 +/- 0.3 microC for remifentanil treatment; n = 12-15; P < 0.05). However, remifentanil did not significantly change Km. Treatment of the oocytes with phorbol-12-myristate-13-acetate (PMA), a PKC activator, caused a significant increase in transporter current (1.00 +/- 0.03 to 1.35 +/- 0.03microC; P < 0.05). Oocytes pretreated with the PKC inhibitor alone (staurosporine) abolished remifentanilenhanced EAAC1 activity. CONCLUSIONS: Our data suggests that remifentanil enhances EAAC1 activity and that PKC is involved in mediating this effect.
Key Words: excitatory amino acid carrier 1, glutamate transporter, protein kinase C, remifentanil, Xenopus oocyte
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