Antidiabetic sulfonylureas: localization of binding sites in the brain and effects on the hyperpolarization induced by anoxia in hippocampal slices.
The distribution of antidiabetic sulfonylurea [( 3H]glibenclamide) binding sites is heterogeneous in rat brain. Pyramidal and extrapyramidal motor system contain the highest densities of sites, particularly in the substantia nigra and in the globus pallidus. Only low levels are present in the hypothalamic nuclei and the main medulla oblongata regions. In hippocampal formation the stratum lucidum and the stratum lacunosum moleculare of CA3 show an important density of glibenclamide binding sites. Electrophysiological studies with hippocampal slices show that glibenclamide blocks hyperpolarization induced by anoxia, suggesting the involvement of adenosine triphosphate-sensitive K+ channel in this early hyperpolarization event.
Mourre
C
C
Centre de Biochimie, Centre National de la Recherche Scientifique, Nice, France.
Ben Ari
Y
Y
Bernardi
H
H
Fosset
M
M
Lazdunski
M
M
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005905:Glyburide / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010101:Oxygen Consumption; D051381:Rats; D013453:Sulfonylurea Compounds / Q000378:metabolism* / Q000494:pharmacology
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D005905:Glyburide