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J Neurophysiol 91: 2385-2388, 2004. First published December 24, 2003; doi:10.1152/jn.01140.2003
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Evidence That Phospholipase D Activation Prevents Group I mGluR-Induced Persistent Prolongation of Epileptiform Bursts

Marjorie J. Rico1 and Lisa R. Merlin1,2,3

1Neural and Behavioral Science Program, School of Graduate Studies and Departments of 2Neurology and 3Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203

Submitted 1 December 2003; accepted in final form 16 December 2003

Selective activation of group I metabotropic glutamate receptors (mGluRs) with (S)-3,5-dihydroxyphenylglycine (DHPG) in guinea pig hippocampal slices converts 275- to 475-ms picrotoxin-induced interictal bursts into persistent seizure-length discharges typically over 1 s in duration. Here we report that L-cysteine sulfinic acid (CSA), a sulfur-containing amino acid, prevented the induction of this persistent group I mGluR-mediated epileptiform burst prolongation. However, CSA had no effect on baseline interictal bursting activity and failed to suppress the expression of the group I mGluR-induced persistent prolonged bursts once they were fully induced. (2R,1'S,2'R,3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), a selective antagonist at the phospholipase D (PLD)-coupled mGluR, had no effect of its own on DHPG-induced burst prolongation; however, CSA applied in the presence of PCCG-13 could no longer fully block the burst prolongation induced by DHPG, suggesting that CSA's antiepileptogenic effect is mediated by agonist action at this PLD-coupled receptor. These data parallel our previous data revealing that protein synthesis inhibitors prevent induction but not expression of group I mGluR-mediated persistent seizure-length discharges. Hence, PLD activation with CSA may prevent the synthesis of a protein critical for the induction of group I mGluR-mediated epileptogenesis.


Address for reprint requests and other correspondence: L. R. Merlin, SUNY Downstate Medical Center, 450 Clarkson Ave., Box 29, Brooklyn, NY 11203 (E-mail: lisa.merlin{at}downstate.edu).




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J. C. Cuellar, E. L. Griffith, and L. R. Merlin
Contrasting Roles of Protein Kinase C in Induction Versus Suppression of Group I mGluR-Mediated Epileptogenesis In Vitro
J Neurophysiol, November 1, 2005; 94(5): 3643 - 3647.
[Abstract] [Full Text] [PDF]




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