Differential actions of 3-(4-chlorophenyl) glutamic acid stereoisomers and l-trans-pyrrolidine-2,4-dicarboxylic acid upon l-homocysteic acid- and l-glutamic acid-induced responses from rat spinal motoneurones

Diastereoselective Synthesis of All Four Isomers of 3-(4-Chlorophenyl)glutamic Acid: Identification of the Isomers Responsible for the Potentiation of l-Homocysteic Acid-Evoked Depolarizations in Neonatal Rat Motoneurons

“…In contrast, responses induced by l -Glu (50 μM) were not affected by any of the four isomers applied at 100 μM, nor by the (2 S ,3 S )- or (2 S ,3 R )-isomers ( 7 and 8 , respectively) at 500 μM. The l -Glu uptake inhibitor, l - trans -pyrrolidine-2,4-dicarboxylic acid, at a concentration of 500 μM, significantly enhanced the depolarizations evoked by both l -HCA (10 μM) and l -Glu (50 μM), although its potentiating action on l -Glu-evoked responses (+160%) was markedly greater than that on l -HCA-induced responses (+22%) 3 Effects of isomers 5−8 (100 μM each) upon 10 μM l -HCA-induced depolarizations.…”

“…Pharmacology. Amino acid-induced depolarizations were recorded from the ventral roots of isolated hemisected spinal cords from 1−5-day old neonatal rats as previously described …”

“…It was found that the (2 R ,3 S )-isomer 5 (100 μM) was effective at reversing a sustained depolarization induced by continuous application of 5 μM NMDA, but was approximately 300-fold weaker than d -2-amino-5-phosphonopentanoate in this regard. None of the stereoisomers, 5−8 (at a concentration of 100 μM), had any effect on depolarizations induced by either ( S )-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (( S )-AMPA; 0.4 μM) or kainic acid (2 μM) and only the (2 R ,3 S )-isomer 5 antagonized NMDA-induced depolarizations (see above) …”

“…Pharmacology 19 Both the (2S,3S)-and (2S,3R)-isomers (7 and 8, respectively) at a concentration of 100 µM significantly potentiated depolarizations induced by 10 µM L-HCA (% control ( sem: 130.4 ( 3.6, n ) 20 and 114.5 ( 2.4, n ) 11, respectively) while the (2R,3S)-isomer 5 significantly reduced L-HCA response amplitude (94.2 ( 1.4, n ) 9) and the (2R,3R)-isomer 6 was inactive (Figure 3). In contrast, responses induced by L-Glu (50 µM) were not affected by any of the four isomers applied at 100 µM, nor by the (2S,3S)-or (2S,3R)-isomers (7 and 8, respectively) at 500 µM.…”

“…The L-Glu uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxylic acid, at a concentration of 500 µM, significantly enhanced the depolarizations evoked by both L-HCA (10 µM) and L-Glu (50 µM), although its potentiating action on L-Glu-evoked responses (+160%) was markedly greater than that on L-HCA-induced responses (+22%). 19 The depressant activity of the (2R,3S)-isomer 5 upon L-HCA-evoked depolarizations was likely to be the result of N-methyl-D-aspartate (NMDA) receptor antagonism, as responses induced by 10 µM L-HCA under these experimental conditions would be mainly the result of NMDA receptor activation. 16 It was found that the (2R,3S)-isomer 5 (100 µM) was effective at reversing a sustained depolarization induced by continuous application of 5 µM NMDA, but was approximately 300-fold weaker than D-2-amino-5-phosphonopentanoate in this regard.…”