Evidence that phospholipase D activation prevents group I mGluR-induced persistent prolongation of epileptiform bursts.

Abstract

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.

• Authors: Marjorie J Rico, Lisa R Merlin
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 91 Issue 5 Pg. 2385-8 (May 2004) ISSN: 0022-3077 [Print] United States
• PMID: 14695353 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 2-(2'-carboxy-3'-phenylcyclopropyl)glycine
• Cyclopropanes
• GABA Antagonists
• GABA-A Receptor Antagonists
• Neurotransmitter Agents
• Receptors, Metabotropic Glutamate
• metabotropic glutamate receptor type 1
• Picrotoxin
• Methoxyhydroxyphenylglycol
• Phospholipase D
• Cysteine
• Glycine
• 3,4-dihydroxyphenylglycol
• cysteine sulfinic acid

Topics

• Animals
• Cyclopropanes (pharmacology)
• Cysteine (analogs & derivatives, pharmacology)
• Epilepsy (physiopathology)
• GABA Antagonists (pharmacology)
• GABA-A Receptor Antagonists
• Glycine (analogs & derivatives, pharmacology)
• Guinea Pigs
• Methoxyhydroxyphenylglycol (analogs & derivatives, pharmacology)
• Neurotransmitter Agents (pharmacology)
• Phospholipase D (metabolism)
• Picrotoxin (pharmacology)
• Receptors, Metabotropic Glutamate (physiology)