The hypoglycemic sulphonylurea tolbutamide increases N-methyl-D-aspartate- but not kainate-activated currents in hippocampal neurons in culture.
The effects of the hypoglycemic sulphonylurea tolbutamide, a marker of K(+)-ATP channels, on the N-methyl-D-aspartate- (NMDA) and kainate-activated currents were studied in rat hippocampal neurons in culture, using the patch-clamp technique in a whole-cell configuration. Tolbutamide (500 microM) reversibly increased the peak amplitude and the steady state level of NMDA- but not kainate-evoked currents. This effect was not glycine dependent as it was observed at low and saturated concentrations of glycine. The affinity of the NMDA receptor-channel complex for glycine did not change in the presence of tolbutamide. The action of tolbutamide on the NMDA-activated current was not mediated by K(+)-ATP channels since CsCl was added intracellularly at concentrations which completely blocked all K+ channels. Possible mechanisms explaining the effect of tolbutamide via the modulation of intracellular messengers are discussed.
Kwiecien
R
R
Laboratoire de Neurobiologie et Physiopathologie du Développement, INSERM U29 123, Paris, France.
Medina
I
I
Barbin
G
G
Ben-Ari
Y
Y
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004594:Electrophysiology; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007608:Kainic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014044:Tolbutamide / Q000494:pharmacology*
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D014044:Tolbutamide; D007608:Kainic Acid; D005998:Glycine