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Doxepin and imipramine but not fluoxetine reduce the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes

Title
Doxepin and imipramine but not fluoxetine reduce the activity of the rat glutamate transporter EAAT3 expressed in Xenopus oocytes
Authors
Park, Hye JinBaik, Hee JungKim, Dong YeonLee, Guie YongWoo, Jae HeeZuo, ZhiyiChung, Rack Kyung
Ewha Authors
이귀용정락경김동연백희정우재희
SCOPUS Author ID
이귀용scopus; 정락경scopus; 김동연scopus; 백희정scopus; 우재희scopus
Issue Date
2015
Journal Title
BMC ANESTHESIOLOGY
ISSN
1471-2253JCR Link
Citation
vol. 15
Publisher
BIOMED CENTRAL LTD
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Background: Many researchers have suggested that the glutamatergic system may be involved in the effects of antidepressant therapies. We investigated the effects of doxepin, imipramine, and fluoxetine on the excitatory amino acid transporter type 3 (EAAT3). Methods: EAAT3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. Membrane currents were recorded after application of L-glutamate (30 mu M) in the presence or absence of various concentrations of doxepin, imipramine, and fluoxetine. To study the effects of protein kinase C (PKC) activation on EAAT3 activity, oocytes were pre-incubated with phorbol 12-myristate-13-acetate (PMA) before application of imipramine and doxepin. Results: Doxepin at 0.063-1.58 mu M significantly decreased EAAT3 activity. Imipramine reduced EAAT3 activity in a concentration-dependent manner at 0.16-0.95 mu M. However, fluoxetine did not affect EAAT3 activity, and PMA increased EAAT3 activity. At 0.32 mu M, imipramine caused an equivalent decrease in EAAT3 activity in the presence or absence of PMA. However, 0.79 mu M doxepin did not abolish the enhancement of EAAT3 activity by PMA. Conclusions: We showed that doxepin and imipramine, but not fluoxetine, inhibited EAAT3 activity at clinically relevant concentrations. This reveals a novel mechanism of action for doxepin and imipramine; that they increase glutamatergic neurotransmission. PKC may be involved in the effects of doxepin on EAAT3, but is not involved in the effects of imipramine at the concentrations studied.
DOI
10.1186/s12871-015-0098-5
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의학전문대학원 > 의학과 > Journal papers
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