Ondansetron attenuates the activity of excitatory amino acid transporter type 3 expressed in Xenopus oocytes

Wonseok Hur, Mi Kyoung Lee, Hee Pyeong Park, Chong Sung Kim, Hea Jo Yoon, Zhiyi Zuo, Sang Hwan Do

Research output: Contribution to journalArticle

Abstract

The purpose of this study was to evaluate the effect of ondansetron on excitatory amino acid transporter type 3 (EAAT3) and to elucidate the roles of protein kinase C (PKC) and phosphatidylinositol 3-kinase (PI3K) in the effect. EAAT3 was expressed in Xenopus oocytes following the injection of rat EAAT3 mRNAs. Using the two-electrode voltage clamping method, the inward currents induced by l-glutamate were measured for 1 min in the presence and absence of ondansetron (1-1000 μM). Different concentrations of l-glutamate (3-300 μM) were used to determine the kinetic characteristics of EAAT3. To identify the involvement of PKC and PI3K in the effect, oocytes were exposed to a PKC activator and to PKC inhibitors and PI3K inhibitors, and l-glutamate-induced currents were recorded. Ondansetron decreased EAAT3 activity in a dose-dependent manner. In a kinetic study, ondansetron (10 μM for 3 min) reduced V max, but not Km compared with the control group. The PKC activator abolished the ondansetron-induced decrease in EAAT3 activity. The PKC inhibitors (staurosporine and chelerythrine) and ondansetron had not additive or synergistic effects on EAAT3 activity. The PI3K inhibitors (wortmannin and LY294002) decreased the EAAT3 response, although there were no differences among the groups comprising ondansetron, PI3K inhibitors, and PI3K inhibitors plus ondansetron. Our results demonstrate that ondansetron attenuates EAAT3 activity and this effect seems to be mediated by PKC and PI3K.

Original languageEnglish
Pages (from-to)7-12
Number of pages6
JournalEuropean Journal of Pharmacology
Volume733
Issue number1
DOIs
Publication statusPublished - 2014 Jun 15

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Excitatory Amino Acid Transporter 3
Ondansetron
Phosphatidylinositol 3-Kinase
Xenopus
Oocytes
Protein Kinase C
Glutamic Acid
Protein C Inhibitor
Protein Kinase Inhibitors
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Staurosporine
Constriction

Keywords

  • EAAT3
  • Glutamate transporter
  • Ondansetron
  • Phosphatidylinositol 3-kinase
  • Protein kinase C
  • Xenopus oocyte

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ondansetron attenuates the activity of excitatory amino acid transporter type 3 expressed in Xenopus oocytes. / Hur, Wonseok; Lee, Mi Kyoung; Park, Hee Pyeong; Kim, Chong Sung; Yoon, Hea Jo; Zuo, Zhiyi; Do, Sang Hwan.

In: European Journal of Pharmacology, Vol. 733, No. 1, 15.06.2014, p. 7-12.

Research output: Contribution to journalArticle

Hur, Wonseok ; Lee, Mi Kyoung ; Park, Hee Pyeong ; Kim, Chong Sung ; Yoon, Hea Jo ; Zuo, Zhiyi ; Do, Sang Hwan. / Ondansetron attenuates the activity of excitatory amino acid transporter type 3 expressed in Xenopus oocytes. In: European Journal of Pharmacology. 2014 ; Vol. 733, No. 1. pp. 7-12.
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