Potentiation of NMDA and AMPA responses by the specific mGluR5 agonist CHPG in spinal cord motoneurons.
The specific metabotropic glutamate receptor (mGluR)5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) is able to potentiate NMDA and AMPA responses recorded from ventral roots of the isolated hemisected baby rat spinal cord. Previously we have demonstrated that activation of group I mGluRs (mGluR1 and mGluR5) with the broad spectrum mGluR agonist 1S,3R-1-amino-1,3-cyclopentanedicarboxylate (ACPD) produced potentiation of ionotropic glutamate responses. In contrast to ACPD-induced potentiation, however, no evidence for an involvement of protein kinase C (PKC) is found in the CHPG-induced potentiation of both NMDA and AMPA depolarization because the PKC blockers chelerythrine chloride or calphostin C did not antagonize this effect. Moreover, in the absence of Ca2+ in the perfusing medium or depleting intracellular Ca2+ stores with thapsigargin or dantrolene did not modify the CHPG-induced enhancement of NMDA depolarizations. Phorbol-12,13-diacetate (PDA), on the other hand, was able to attenuate this effect, which was reversed by chelerythrine chloride. These results suggest that both mGluR5 and mGluR1 may act to enhance ionotropic glutamate responses but the two types of mGluRs may have different intracellular mechanisms of action.
Ugolini
A
A
Pharmacology Department, GlaxoWellcome Medicines Research Centre, Verona, Italy.
Corsi
M
M
Bordi
F
F
D000470:Alkaloids; D000818:Animals; D000831:Animals, Newborn; D053119:Benzophenanthridines; D002118:Calcium / Q000378:metabolism; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D016202:N-Methylaspartate / Q000494:pharmacology*; D010617:Phenanthridines / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D013116:Spinal Cord / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
C107349:2-chloro-5-hydroxyphenylglycine; D000470:Alkaloids; D053119:Benzophenanthridines; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D010617:Phenanthridines; D010648:Phenylacetates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C016299:chelerythrine; D002118:Calcium; D005998:Glycine