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.
Department of Physiology and Pathophysiology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai 200032, People's Republic of China.
Ying
Y
Huang
Ya-Lin
YL
Huang
Sun
S
Zhang
Yi-Chun
YC
Zhu
Tai
T
Yao
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