Differential effects of allopregnanolone and GABA on kainate-induced lactate dehydrogenase release in cultured rat cerebral cortical cells.
OBJECTIVE
To exam the effects of allopregnanolone and gamma-amino-butyric acid (GABA) on the excitotoxicity.


METHODS
The excitotoxicity was evoked by kainate (KA) in the primary culture of rat cerebral cortical cells. Effect of allopregnanolone or GABA on the excitotoxicity was examined by the measurement of lactate dehydrogenase (LDH) activity released in the culture medium.


RESULTS
Either acute (3 h) or chronic (24 h) treatment with KA (0.01-1 mmol/L) produced a concentration-dependent increase in LDH activity released. The EC50 values were (0.16+/-0.03) mmol/L and (0.257+/-0.015) mmol/L, respectively. Acute treatment with allopregnanolone (10-1000 nmol/L) for 3 h did not significantly affect the 0.2 mmol/L KA-induced LDH activity. On the other hand, chronic treatment with allopregnanolone (10-1000 nmol/L) for 24 h, produced inhibition on the KA-induced LDH activity in a concentration-dependent manner. The EC50 value was (436+/-19) nmol/L. Acute treatment with GABA (0.1-100 micromol/L) exacerbate the 0.2 mmol/L KA-induced LDH activity in a concentration-dependent manner, with an EC50 value of (2.7+/-1.0) micromol/L; while chronic treatment with GABA had no significant effect.


CONCLUSIONS
There were differential patterns between the effects of allopregnanolone and GABA on the KA-induced excitotoxicity.
Yu
Rong
R
Department of Pharmacology, Medical Center, Fudan University, Shanghai 200032, China. ryu@shmu.edu.cn
Xu
Xin-Hong
XH
Sheng
Mei-Ping
MP
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D005680:gamma-Aminobutyric Acid; D011280:Pregnanolone; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid