|
Copyright © 1998 by Institute of Pharmacology Polish Academy of Sciences |
Pol. J. Pharmacol., 1998, 50, 355-360 ISSN 1230-6002 |
|
Effect of neurosteroids on glutamate binding sites and glutamate uptake in rat hippocampus.
M. LEŚKIEWICZ, B. BUDZISZEWSKA, L. JAWORSKA-FEIL, M. KAJTA, W. LASOŃ. Pol. J. Pharmacol., 1998, 50, 355-360. Effects of some neurosteroids on the binding of [3H]-glutamate, [3H]-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and [3H]-MK-801, as well as on the [3H]-glutamate uptake were examined in rat hippocampus. The following compounds were evaluated: (a) positive modulators of the GABAA receptor: 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone), alpha-pregnane-3alpha,21-diol-20-one (allotetrahydrodeoxycorticosterone), 5alpha-pregnan-3alpha-ol-11,20-dione (alphaxalone) and 5alpha-androstan-3alpha-ol-17-one (androsterone); (b) compounds showing GABAA-antagonistic and/or N-methyl-D-aspartic acid (NMDA)-agonistic properties: dehydroepiandrosterone sulfate and pregnenolone sulfate; (c) a substance which, apart from its GABAA-agonistic potency, has a NMDA-antagonistic action: 5beta-pregnan-3alpha-ol-20-one. None of those neurosteroids tested at concentrations of 0.001-100 µM affected the binding of [3H]-glutamate, [3H]-AMPA and [3H]-MK-801 or the glutamate uptake. The present study suggests that the previously reported inhibitory effects of neurosteroids on excitatory amino acid-induced seizures and neurotoxicity can be linked neither to the direct interaction of these compounds with the above binding sites on glutamate receptor complexes, nor to the glutamate uptake mechanism. Key words: reactive oxygen metabolites, lung, BN 52021, PAF-receptor antagonist, haemorrhagic shock |
| Back to: Top | PJP - Home Page | |