Estradiol acutely attenuates glutamate-induced calcium overload in primarily cultured rat hippocampal neurons through a membrane receptor-dependent mechanism.
Increasing lines of evidence indicate that estrogen acts as a neuroprotective agent through a nongenomic mechanism. We tested the hypothesis that 17beta-estradiol could rapidly attenuate glutamate-induced calcium (Ca2+) overload in rat primary hippocampal neurons via a membrane receptor-dependent mechanism. The bulk cytosolic intracellular Ca2+ level was measured in neurons with fluorescent Ca2+ probe fluo3. Preexposure of primary cultured hippocampal neurons to 17beta-estradiol for 3 min attenuated intracellular Ca2+ increase induced by glutamate in a concentration-dependent manner. The action of 17beta-estradiol was reversible after washout. Administration of membrane-impermeable 17beta-estradiol conjugated to bovine serum albumin (E2-BSA) produced the same effect, suggesting possible involvement of cell membrane receptors. ICI 182,780, a specific estrogen receptor (ER) antagonist, blocked the neuronal response to 17beta-estradiol and estradiol BSA, indicating a role of specific ERs. The present study demonstrates that 17beta-estradiol acutely reduces glutamate-stimulated intracellular Ca2+ increase via ERs probably on the cell surface of the hippocampal neurons.
Huang
Ying
Y
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China.
Huang
Ya-Lin
YL
Zhang
Sun
S
Zhu
Yi-Chun
YC
Yao
Tai
T
D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014966:Xanthenes / Q000378:metabolism
D000814:Aniline Compounds; D011956:Receptors, Cell Surface; D014966:Xanthenes; C043090:estradiol-bovine serum albumin; C059715:Fluo-3; D012710:Serum Albumin, Bovine; D018698:Glutamic Acid; D004958:Estradiol; D002118:Calcium