Characterization and localization of [3H] cyclosporin A binding sites in rat brain.
The immunosuppressant drug [3H]cyclosporin A binds specifically and with high affinity to rat brain membrane preparations. The highest density of binding sites was observed in the hippocampus, cerebellum, cortex and basal ganglia. A similar distribution pattern was seen using a quantitative autoradiographic analysis. This distribution agrees with the localizations of cyclophilin and calcineurin reported in immunohistochemical and in situ hybridization studies. Thus inhibition of calcineurin activity following cyclosporin A binding to cyclophilin may occur in neurones, as it does in T-cells. These results suggest that the neurological side-effects of cyclosporin A may be mediated through its interaction with these proteins in neurones.
Bladen
C
C
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Vincent
S R
SR
D000591:Amino Acid Isomerases / Q000032:analysis*; D000818:Animals; D001479:Basal Ganglia / Q000378:metabolism / Q000648:ultrastructure; D001923:Brain Chemistry; D019703:Calcineurin; D002122:Calcium Chloride / Q000494:pharmacology; D002148:Calmodulin-Binding Proteins / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis*; D002531:Cerebellum / Q000378:metabolism / Q000648:ultrastructure; D016572:Cyclosporine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000032:analysis*; D051381:Rats; D011971:Receptors, Immunologic / Q000032:analysis* / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D011971:Receptors, Immunologic; D013449:Sulfonamides; C028752:cyclosporin receptor; C017967:W 7; D016572:Cyclosporine; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase; D002122:Calcium Chloride