DIFFERENTIAL ACTIONS OF 3-(4-CHLOROPHENYL) GLUTAMIC-ACID STEREOISOMERS AND L-TRANS-PYRROLIDINE-2,4-DICARBOXYLIC ACID UPON L-HOMOCYSTEIC ACID-INDUCED AND L-GLUTAMIC ACID-INDUCED RESPONSES FROM RAT SPINAL MOTONEURONS

The four recently synthesized stereoisomers of 3-(4-chlorophenyl) glut amic acid (chlorpheg) were individually examined for their abilities t o potentiate depolarizations of neonatal rat motoneurones evoked by L- homocysteic acid (L-HCA, 10 mu M). This property had previously been o bserved using the racemate and is believed to be mediated by uptake in hibition. Both the (2S,3S)- and (2S,3R)- isomers were selective potent iators of L-HCA-(vs L-Glu) induced depolarizations although the (2S,3S )- isomer was more effective. The(2R,3S)- isomer had a slight but sign ificant depressant action which could be attributed to N-methyl-D-aspa rtate (NMDA) receptor antagonism. Comparison of the potentiating prope rties of (2S,3S)- and (2S,3R)-chlorpheg with those of L-trans-pyrrolid ine-2,4-dicarboxylic acid (tPDC, a L-Glu uptake inhibitor) upon L-HCA- and L-Glu-evoked responses revealed that both chlorpheg isomers (500 mu M each) selectively potentiated responses evoked by L-HCA (10 M mu) but had no significant effect upon those evoked by L-Glu (50 mu M). O n the other hand, use of tPDC at the same concentration significantly enhanced the depolarizations evoked by both amino acids, although its action on L-Glu-evoked responses was greater. It is concluded that (i) the (2S,3S)- isomer and to a lesser extent, the (2S,3R)- isomer of ch lorpheg are responsible for the potentiating actions seen with the chl orpheg racemate used in previous studies and (ii) (2R,3S)-chlorpheg is a weak NMDA antagonist. The apparently selective action of (2S,3S)- a nd (2S,3R)-chlorpheg upon L-HCA- relative to L-Glu-induced depolarizat ions supports the existence of multiple excitatory amino acid uptake s ites, some of which may yet be unidentified.