title: Effect of neurosteroids on glutamate binding sites and glutamate uptake in rat hippocampus.
abstract: 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 GABA(A) receptor: 5alpha-pregnan-3alpha-ol-20-one (allopregnanolone), 5alpha-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 GABA(A)-antagonistic and/or N-methyl-D-aspartic acid (NMDA)-agonistic properties: dehydroepiandrosterone sulfate and pregnenolone sulfate; (c) a substance which, apart from its GABA(A)-agonistic potency, has a NMDA-antagonistic action: 5beta-pregnan-3alpha-ol-20-one. None of those neurosteroids tested at concentrations of 0.001-100 microM 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.
authors: Department of Endocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors: M
authors: M
authors: Leśkiewicz
authors: B
authors: B
authors: Budziszewska
authors: L
authors: L
authors: Jaworska-Feil
authors: M
authors: M
authors: Kajta
authors: W
authors: W
authors: Lasoń
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000378:metabolism*; D004347:Drug Interactions; D018846:Excitatory Amino Acids / Q000633:toxicity; D018755:GABA Agonists; D018756:GABA Antagonists; D018698:Glutamic Acid / Q000493:pharmacokinetics / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009420:Nervous System / Q000187:drug effects; D011280:Pregnanolone; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism*
chemical_list: D018846:Excitatory Amino Acids; D018755:GABA Agonists; D018756:GABA Antagonists; D018079:Receptors, GABA; D017470:Receptors, Glutamate; D013256:Steroids; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011280:Pregnanolone; D005998:Glycine