Allosteric potentiation by diazoxide of AMPA receptor currents and synaptic potentials
| Autor: | Catherine Biton, Jean M. Lepagnol, John C.R. Randle |
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| Rok vydání: | 1993 |
| Předmět: |
Agonist
Male medicine.medical_specialty N-Methylaspartate medicine.drug_class Xenopus Glycine Kainate receptor AMPA receptor Biology In Vitro Techniques Hippocampus Membrane Potentials chemistry.chemical_compound Allosteric Regulation Internal medicine medicine Diazoxide Animals RNA Messenger Receptors AMPA Rats Wistar gamma-Aminobutyric Acid Pharmacology Long-term potentiation Potassium channel Rats Inbred F344 Rats Kinetics Endocrinology chemistry Synapses Excitatory postsynaptic potential Oocytes NBQX medicine.drug |
| Zdroj: | European journal of pharmacology. 247(3) |
| ISSN: | 0014-2999 |
| Popis: | Diazoxide (100-560 microM) reversibly increased the amplitude and duration of excitatory post-synaptic field potentials recorded in the dentate gyrus of hippocampal slices following stimulation of the perforant pathway. In rat cortex mRNA-injected Xenopus oocytes diazoxide (1-1000 microM) alone had little effect on membrane current, but rapidly and reversibly increased (up to 5-fold) current responses to (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA, 30 microM), L-glutamate (100 microM), quisqualate (3 microM), kainate (100 microM) and domoate (3 microM), an effect that was neither mimicked by other activators of ATP-sensitive potassium channels nor blocked by glibenclamide. Diazoxide increased current amplitudes for all concentrations of the 'inactivating' ligands, AMPA, L-glutamate and quisqualate but had little effect on their EC50 values. In contrast, diazoxide increased the apparent potency of the 'non-inactivating' ligands, kainate and domoate, but increased the efficacy of saturating concentrations by only 10-20%. Diazoxide did not modify the competitive inhibition of AMPA and kainate currents by 6-nitro-7-sulfamoylbenzo[f]quinoxaline-2,3-dione (NBQX) and thus does not compete for the agonist site as do AMPA and kainate. Similarly, diazoxide neither inhibited the binding of [3H]AMPA or [3H]kainate to rat cortical membranes in competition experiments nor consistently modified the apparent [3H]AMPA affinity (Kd) or receptor density (Bmax) in saturation experiments. These data suggest that diazoxide acts at an allosteric site on the AMPA receptor/channel to potentiate activation in a manner dependent upon the properties of the excitatory agonist. |
| Databáze: | OpenAIRE |
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