Allosteric potentiation of quisqualate receptors by a nootropic drug aniracetam.
1. Allosteric potentiation of the ionotropic quisqualate (iQA) receptor by a nootropic drug aniracetam (1-p-anisoyl-2-pyrrolidinone) was investigated using Xenopus oocytes injected with rat brain mRNA and rat hippocampal slices. 2. Aniracetam potentiates the iQA responses induced in Xenopus oocytes by rat brain mRNA in a reversible manner. This effect was observed above the concentrations of 0.1 mM. Kainate. N-methyl-D-aspartate and gamma-aminobutyric acid responses induced in the same oocytes were not affected. 3. The specific potentiation of iQA responses was accompanied by an increase in the conductance change of iQA and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) responses, but the affinity of receptors for agonist and the ion-selectivity of the channels (reversal potentials) were not changed. 4. Aniracetam reversibly potentiated the iQA responses recorded intracellularly from the pyramidal cells in the CA1 region of rat hippocampal slices. The excitatory postsynaptic potentials (EPSPs) in Schaffer collateral-commissural-CA1 synapses were also potentiated by aniracetam. 5. Population EPSPs recorded in the mossy fibre-CA3 synapses as well as Schaffer-commissural synapses were also potentiated by aniracetam. The amplitudes of the potentiation were not changed by the formation of long-term potentiation.
Ito
I
I
Fujigotemba Research Laboratories, Chugai Pharmaceutical Company, Gotemba, Japan.
Tanabe
S
S
Kohda
A
A
Sugiyama
H
H
D000200:Action Potentials / Q000187:drug effects; D000494:Allosteric Regulation; D000818:Animals; D001923:Brain Chemistry; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects; D011061:Poly A / Q000235:genetics / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000235:genetics; D013569:Synapses / Q000187:drug effects; D014982:Xenopus laevis
D011061:Poly A; D011760:Pyrrolidinones; D012333:RNA, Messenger; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C036466:aniracetam