Distinctions between persistent and reversible group I mGluR-induced epileptiform burst prolongation.
We have previously shown that selective activation of group I metabotropic glutamate receptors (mGluRs) results in long-lasting enhancement of synchronized network activity in the hippocampal slice. Data herein suggest that activation of group I mGluRs need not result in this potentially epileptogenic effect. (1S,3R)-1-Aminocyclopentane-1,3-dicarboxylic acid (ACPD), a nonselective mGluR agonist, elicits ictaform bursts identical in appearance to those induced by selective agonists, but ACPD-induced bursts do not persist following removal of the agent. Like the bursts induced by selective agonist, the ACPD bursts are blocked with group I mGluR antagonists and are not dependent on activation of either N-methyl-D-aspartate (NMDA) receptors or protein kinase C. However, they differ from the persistent bursts in that they do not require active protein synthesis and they are not suppressed with L-cysteine sulfinic acid, an agonist at a phospholipase D-coupled metabotropic receptor. These novel findings provide evidence that group I mGluR-induced epileptogenesis may be preventable.
Fuortes
Michaelangelo G
MG
Neural and Behavioral Sciences Program, School of Graduate Studies, SUNY Downstate Medical Center, Brooklyn, NewYork, USA.
Rico
Marjorie J
MJ
Merlin
Lisa R
LR
D000704:Analysis of Variance; D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D053119:Benzophenanthridines / Q000494:pharmacology; D004148:Dioxolanes / Q000494:pharmacology; D004357:Drug Synergism; D018756:GABA Antagonists / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D010739:Phospholipase D / Q000378:metabolism; D010852:Picrotoxin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000841:Anisomycin; D053119:Benzophenanthridines; D004148:Dioxolanes; D018756:GABA Antagonists; D008734:Methoxyhydroxyphenylglycol; D010739:Phospholipase D; D010852:Picrotoxin; D011500:Protein Synthesis Inhibitors; D011687:Purines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C104068:4-(2-amino-6-chloro-9H-purin-9-yl)-1,3-dioxolane-2-methanol; C016299:chelerythrine; C010117:3,4-dihydroxyphenylglycol