title: Brain ischemia alters the density of binding sites for glibenclamide, a specific blocker of ATP-sensitive K+ channels.
abstract: Transient ischemia in normoglycemic animals leads to delayed neuronal damage which is confined to selectively vulnerable regions. In at least one of these, the CA1 sector of the hippocampus, cell death is preceded by neuronal hyperactivity, presumed to be caused by loss of inhibitory control. Hyperglycemic subjects develop postischemic seizures, and show enhanced damage. The ATP-sensitive K+ channel, which may be important in inhibitory control, is the target of antidiabetic sulfonylureas. We determined densities of sulfonylurea binding sites in rat brain after forebrain ischemia. Normoglycemic animals showed a decrease of glibenclamide receptor binding in the CA3 field, hilus and dentate gyrus of the hippocampus after 1 day of recovery. After 4 days of recovery, levels of sulfonylurea binding sites decreased mainly in the CA1 field and in the hilus, as well as in the substantia nigra. After 1 day of recovery, hyperglycemic animals did not show any significant variations of densities of sites compared to control animals. It is proposed that reduction of inhibitory control by ATP-sensitive K+ channels may be associated with delayed neuronal death.
authors: Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 du CNRS, Valbonne, France.
authors: C
authors: C
authors: Mourre
authors: M L
authors: ML
authors: Smith
authors: B K
authors: BK
authors: Siesjö
authors: M
authors: M
authors: Lazdunski
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005905:Glyburide / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism*
chemical_list: D015221:Potassium Channels; D011955:Receptors, Drug; C067662:glibenclamide receptor; D000255:Adenosine Triphosphate; D005905:Glyburide