Article date: October 1991
By: J.P. Turner, B.S. Meldrum, in Volume 104, Issue 2, pages 445-451
The effects of l‐glutamate diethyl ester (GDEE) HCl, glutarate diethyl ester (GlrDEE) and glutarate dimethyl ester (GlrDME) on depolarizing responses to α‐amino‐3‐hydroxy‐5‐methyl‐4‐iso‐xazolepropionate (AMPA), kainate (Kain), N‐methyl‐d‐aspartate (NMDA) and quisqualate (Quis), and spontaneous paroxsymal discharges (SPDs) were examined. Experiments were performed on slices of rat cingulate cortex using the in vitro grease gap recording technique in nominally Mg2+‐free Krebs medium.
GDEE HCl (3–14 mm) caused a concentration‐dependent depolarization of the d.c. baseline potential. l‐Glutamate (0.1–0.5 mm), HCl (15 mm) and sucrose (30 mm) also depolarized the baseline. GlrDEE (3–12 mm) and GlrDME (4–26 mm) had no consistent effect on baseline potential.
GDEE HCl (10 mm) had no effect on depolarizing responses to AMPA, Kain and NMDA, but caused potentiation of those to Quis with a dose‐ratio of 0.53 (0.44–0.63) (n = 4). In two other experiments, where the depolarization of the baseline induced by GDEE HCl was large, a depression of Quis response amplitude was observed.
GlrDEE (10 mm) antagonized depolarizing responses to Kain, and to a lesser extent NMDA, with dose‐ratios of 2.14 (1.92–2.38) and 1.61 (1.39–1.87), respectively. This concentration of GlrDEE had no effect on AMPA responses, but potentiated Quis responses, with a dose‐ratio of 0.64 (0.58–0.71).
GlrDME (10 mm) antagonized depolarizing responses to Kain and to Quis, with dose‐ratios of 1.66 (1.48–1.85) and 1.22 (1.15–1.29), respectively, and had no effect on responses to NMDA.
The SPDs were inhibited by GDEE HCl (IC50 6.7 ± 0.37 mm), GlrDEE (IC50 5.6 ± 0.38 mm) and GlrDME (IC50 10.4 ± 0.73 mm).
In conclusion, there is little evidence that GDEE HCl is an antagonist of the postsynaptic excitatory amino acid receptors in the rat neocortex, and its effects may result from its contamination with l‐glutamate and increased osmolarity of the bathing medium at high concentrations. The deaminated analogues of GDEE are very weak Kain antagonists.
The effects of l‐glutamate diethyl ester (GDEE) HCl, glutarate diethyl ester (GlrDEE) and glutarate dimethyl ester (GlrDME) on depolarizing responses to α‐amino‐3‐hydroxy‐5‐methyl‐4‐iso‐xazolepropionate (AMPA), kainate (Kain), N‐methyl‐d‐aspartate (NMDA) and quisqualate (Quis), and spontaneous paroxsymal discharges (SPDs) were examined. Experiments were performed on slices of rat cingulate cortex using the in vitro grease gap recording technique in nominally Mg2+‐free Krebs medium.
GDEE HCl (3–14 mm) caused a concentration‐dependent depolarization of the d.c. baseline potential. l‐Glutamate (0.1–0.5 mm), HCl (15 mm) and sucrose (30 mm) also depolarized the baseline. GlrDEE (3–12 mm) and GlrDME (4–26 mm) had no consistent effect on baseline potential.
GDEE HCl (10 mm) had no effect on depolarizing responses to AMPA, Kain and NMDA, but caused potentiation of those to Quis with a dose‐ratio of 0.53 (0.44–0.63) (n = 4). In two other experiments, where the depolarization of the baseline induced by GDEE HCl was large, a depression of Quis response amplitude was observed.
GlrDEE (10 mm) antagonized depolarizing responses to Kain, and to a lesser extent NMDA, with dose‐ratios of 2.14 (1.92–2.38) and 1.61 (1.39–1.87), respectively. This concentration of GlrDEE had no effect on AMPA responses, but potentiated Quis responses, with a dose‐ratio of 0.64 (0.58–0.71).
GlrDME (10 mm) antagonized depolarizing responses to Kain and to Quis, with dose‐ratios of 1.66 (1.48–1.85) and 1.22 (1.15–1.29), respectively, and had no effect on responses to NMDA.
The SPDs were inhibited by GDEE HCl (IC50 6.7 ± 0.37 mm), GlrDEE (IC50 5.6 ± 0.38 mm) and GlrDME (IC50 10.4 ± 0.73 mm).
In conclusion, there is little evidence that GDEE HCl is an antagonist of the postsynaptic excitatory amino acid receptors in the rat neocortex, and its effects may result from its contamination with l‐glutamate and increased osmolarity of the bathing medium at high concentrations. The deaminated analogues of GDEE are very weak Kain antagonists.
DOI: 10.1111/j.1476-5381.1991.tb12449.x
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