Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum.
The localization of a putative ATP-regulated K+ channel in normal rat and neurological mutant mice was studied by light microscopic quantitative autoradiography using a tritiated glibenclamide, an antidiabetic sulfonylurea. Glibenclamide binding sites presented a heterogeneous distribution in the rat central nervous system. Their density was particularly important in substantia nigra reticulata, septohippocampal nucleus, globus pallidus, neocortex, molecular layer of cerebellum, CA3 field and dentate gyrus of hippocampus. Conversely hypothalamic areas, medulla oblongata and spinal cord contained only low amounts of glibenclamide receptors. The ontogenesis of sulfonylurea binding sites was a postnatal phenomenon and seemed to correlate with the maturation of neuronal connectivity. In the cerebellum of neurological mutant mice, the autoradiographic patterns were different to that of wild-type cerebellum. In particular, in the molecular layer of weaver cerebellum, a decrease of 82% of binding site density suggested a presynaptic position of glibenclamide receptors in parallel fibers.
Mourre
C
C
Institut de Pharmacologie Moléculaire et Cellulaire, U.P.R. 411 C.N.R.S., Valbonne, France.
Widmann
C
C
Lazdunski
M
M
D018528:ATP-Binding Cassette Transporters; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001921:Brain / Q000254:growth & development* / Q000378:metabolism; D002531:Cerebellum / Q000254:growth & development* / Q000378:metabolism; D005905:Glyburide / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009928:Organ Specificity; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism*; D013045:Species Specificity; D064233:Sulfonylurea Receptors; D014316:Tritium
D018528:ATP-Binding Cassette Transporters; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014316:Tritium; D000255:Adenosine Triphosphate; D005905:Glyburide