CHARACTERIZATION AND LOCALIZATION OF [H-3] CYCLOSPORINE-A BINDING-SITES IN RAT-BRAIN

THE immunosuppressant drug [H-3]cyclosporin A binds specifically and w ith high affinity to rat brain membrane preparations. The highest dens ity of binding sites was observed in the hippocampus, cerebellum, cort ex 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 immunohis tochemical and in situ hybridization studies. Thus inhibition of calci neurin activity following cyclosporin A binding to cyclophilin may occ ur 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.