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

The specific metabotropic glutamate receptor (mGluR)(5) agonist (RS)-2-chlo ro-5-hydroxyphenylglycine (CHPG) is able to potentiate NMDA and AMPA respon ses recorded from ventral roots of the isolated hemisected baby rat spinal cord. Previously we have demonstrated that activation of group I mGluRs (mG luR(1) and mGluR(5)) with the broad spectrum mGluR agonist 1S,3R-1-amino-1, 3-cyclopentanedicarboxylate (ACPD) produced potentiation of ionotropic glut amate responses. In contrast to ACPD-induced potentiation, however, no evid ence for an involvement of protein kinase C (PKC) is found in the CHPG-indu ced potentiation of both NMDA and AMPA depolarization because the PKC block ers chelerythrine chloride or calphostin C did not antagonize this effect. Moreover, in the absence of Ca2+ in the perfusing medium or depleting intra cellular Ca2+ stores with thapsigargin or dantrolene did not modify the CHP G-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 mG luR(1) may act to enhance ionotropic glutamate responses but the two types of mGluRs may have different intracellular mechanisms of action. (C) 1999 E lsevier Science Ltd. All rights reserved.