Potentiation of NMDA and AMPA responses by the specific mGluR 5 agonist CHPG in spinal cord motoneurons

Abstract

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 (mGluR 1 and mGluR 5) with the broad spectrum mGluR agonist 1 S,3 R-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 Ca 2+ in the perfusing medium or depleting intracellular Ca 2+ 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 mGluR 5 and mGluR 1 may act to enhance ionotropic glutamate responses but the two types of mGluRs may have different intracellular mechanisms of action.