Interaction of group I mGlu and NMDA receptor agonists within the dorsal horn of the spinal cord of the juvenile rat.
1. The modulatory effects of mGlu receptors on NMDA-induced potential changes in spinal motoneurones were studied in vitro. 2. Selective activation of mGlu5 receptors by 10 microM (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG; EC(50)=280 +/- 24 microM) did not produce any change in the ventral root potential. However, the same concentration of CHPG (10 min perfusion) significantly attenuated the NMDA-induced ventral root depolarization (VRD). The effect persisted for 10 min after washout. NMDA-induced responses returned to control in 30 min. Brief co-application of CHPG and NMDA did not alter the NMDA-induced response indicating lack of direct receptor interaction. 3. The attenuating effect of CHPG on the NMDA-induced VRD was inhibited by the mGluR5 receptor antagonist, 2-methyl-6-phenyl-ethynylpyridine (MPEP). 4. In the presence of CGP56433A, a GABA(B) receptor antagonist, the NMDA-induced VRD was unchanged. However, NMDA-induced responses were potentiated after 10 min co-application of CHPG and CGP56433A. 5. (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate ((2R,4R)-APDC), a group II mGlu receptor agonist did not attenuate the NMDA-induced response. 6. Under normal physiological conditions group I mGlu receptor agonists activate at least two populations of neurones: (1) GABA-ergic cells, which could release GABA and inhibit dorsal horn neurones, and (2) deep dorsal horn neurones/motoneurones which express NMDA receptors. Therefore, activation of mGlu5 receptors located on GABA-ergic interneurones could influence any direct potentiating interaction between mGlu5 and NMDA receptors in spinal cord and result in depression of the VRD. In the presence of a GABA(B) receptor antagonist, the direct synergistic interaction is unmasked. These data suggest that group I mGlu receptors provide a complex modulation of spinal synaptic processes.
Dang
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Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BN, UK.
Naeem
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S
Walker
K
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Bowery
N G
NG
Urban
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D000818:Animals; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D010648:Phenylacetates / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
C107349:2-chloro-5-hydroxyphenylglycine; D018690:Excitatory Amino Acid Agonists; D058788:GABA-B Receptor Antagonists; D010648:Phenylacetates; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1; D005998:Glycine