1.
Neurosci Lett
; 174(2): 193-7, 1994 Jun 20.
Article
in English
| MEDLINE
| ID: mdl-7970177
ABSTRACT
A series of L-3,4-methanopyrrolidine dicarboxylate isomers were investigated as potential inhibitors of the high affinity, sodium-dependent glutamate transporter in rat forebrain synaptosomes. Of the isomers tested, only L-anti-endo-3,4-methanopyrrolidine dicarboxylate (L-anti-endo-MPDC) blocked the uptake of [3H]D-aspartate, a non-metabolized substrate. Kinetic analysis demonstrated that L-anti-endo-MPDC is a potent competitive inhibitor (Ki = 5 microM) comparable to that of L-glutamate and L-trans-2,4-pyrrolidine dicarboxylate (L-trans-2,4-PDC). Conformational analysis of L-glutamate, L-trans-2,4-PDC and L-anti-endo-MPDC are used to refine the pharmacophore model of the transporter binding site.