Multiple Subtypes of Excitatory Amino Acid Receptors Coupled to the Hydrolysis of Phosphoinositides in Rat Brain

: The excitatory amino acid (EAA) analogues quisqualate, ibotenate, and trans‐(±)‐1‐amino‐1, 3‐cyclopentanedicarboxylate (trans‐ACPD) activate the metabotropic EAA receptors that are coupled to the hydrolysis of Phosphoinositides (PI). Previous studies of hippocampal cross sections demonstrated that...

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Veröffentlicht in:Journal of neurochemistry 1993-08, Vol.61 (2), p.586-593
Hauptverfasser: Littman, Louis, Glatt, Brian S., Robinson, Michael B.
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Sprache:eng
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Zusammenfassung:: The excitatory amino acid (EAA) analogues quisqualate, ibotenate, and trans‐(±)‐1‐amino‐1, 3‐cyclopentanedicarboxylate (trans‐ACPD) activate the metabotropic EAA receptors that are coupled to the hydrolysis of Phosphoinositides (PI). Previous studies of hippocampal cross sections demonstrated that PI hydrolysis stimulated by these agonists can be inhibited by either L‐aspartate‐β‐ hydroxamate (L‐AβHA) or DL‐2‐amino‐3‐phosphonopropionate (DL‐AP3). The goal of the present studies was to determine if all metabotropic EAA receptors are sensitive to L‐AβHA and DL‐AP3. Two approaches were used. In the first, using cerebellar cross sections, the effects of these agonists and inhibitors were examined. The EC50 values (the concentrations required to evoke half‐maximal stimulation) of quisqualate, ibotenate, and trans‐ACPD in cerebellum were similar to the EC50 values that we observed previously in hippocampus, but neither L‐AβHA nor DL‐ AP3 blocked PI hydrolysis. The EC50 values were 0.65 ± 0.17 μM for quisqualate, 12.8 ± 2.5 μM for ibotenate, and 18.1 ± 3.1 μM for trans‐ACPD. All data were best fit to theoretical curves that had Hill slopes of 1. In the second approach, another EAA analogue, D‐aspartate, was identified as an agonist that stimulates PI hydrolysis. The EC50for PI hydrolysis stimulated by D‐aspartate was 470 ± 90 μM in hippocampus. Neither L‐AβSHA nor DL‐AP3 blocked PI hydrolysis stimulated by D‐aspartate in hippocampus. Furthermore, antagonists of ionotropic EAA receptors, antagonists of other receptor systems coupled to PI hydrolysis, and inhibitors of the Na+‐dependent L‐glutamate transport process also did not block PI hydrolysis stimulated by D‐aspartate. These data support the presence of three pharmacologically distinct metabotropic EAA receptor subtypes.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.1993.tb02162.x