Effects of tamoxifen on L-glutamate transporters of astrocytes.
Tamoxifen (Tam) decreased the clearance of L-glutamate (L-Glu) by cultured astrocytes at 1 pM, 1 nM, and 1 microM, but became toxic at 10 microM. When L-Glu transporters were mostly inhibited by threo-beta-benzyloxyaspartate (TBOA) (1 mM) or D,L-threo-beta-hydroxyaspartate (THA) (1 mM), Tam (1 nM) did not change extracellular L-Glu concentration, confirming that Tam attenuates L-Glu transport through L-Glu transporters. ICI182,780, LY294002, and U0126 inhibited the effect of Tam dose-dependently, suggesting the involvement of estrogen receptors (ERs), the phosphatidylinositol 3-kinase (PI3K) cascade, and the mitogen-activated protein kinase (MAPK) cascade in the effect of Tam.
Sato
Kaoru
K
Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan. kasato@nihs.go.jp
Saito
Yoshihiko
Y
Oka
Jun-ichiro
J
Ohwada
Tomohiko
T
Nakazawa
Ken
K
D027322:Amino Acid Transport System X-AG / Q000502:physiology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000502:physiology; D013619:Tacrine / Q000494:pharmacology; D013629:Tamoxifen / Q000494:pharmacology*
D027322:Amino Acid Transport System X-AG; D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; C120673:benzyloxyaspartate; D013629:Tamoxifen; D001224:Aspartic Acid; D018698:Glutamic Acid; D013619:Tacrine; D019869:Phosphatidylinositol 3-Kinases