Inhibition of the rat blood-brain barrier choline transporter by manganesechloride

Choline transport has been characterized by multiple mechanisms including t he blood-brain barrier (BBB), and high- and low-affinity systems. Each mech anism has unique locations and characteristics yet retain some similarities . Previous studies have demonstrated cationic competition by monovalent cat ions at the BBB and cation divalent manganese in the high-affinity system. To evaluate the effects of divalent manganese inhibition as well as other c ationic metals at the BBB choline transporter, brain choline uptake was eva luated in the presence of certain metals of interest in Fischer-344 rats us ing the in situ brain perfusion technique. Brain choline uptake was inhibit ed in the presence of Cd2+ (73 +/- 2%) and Mn2+ (44 +/- 6%), whereas no inh ibition was observed with Cu2+ and Al3+. Furthermore, it was found that man ganese caused a reduction in brain choline uptake and significant regional choline uptake inhibition in the frontal and parietal cortex, the hippocamp us and the caudate putamen (45 +/- 3%, 68 +/- 18%, 58 +/- 9% and 46 +/- 15% , respectively). These results suggest that choline uptake into the CNS can be inhibited by divalent cationic metals and monovalent cations. In additi on, the choline transporter may be a means by which manganese enters the br ain.