Determination of group I metabotropic glutamate receptor subtypes involved in the frequency of epileptiform activity in vitro using mGluR1 and mGluR5 mutant mice.
In mouse hippocampal slices, bicuculline elicited spontaneous epileptiform bursts with a duration of 200-300 ms and with a frequency of five to six events per minute. Application of group I metabotropic glutamate receptor agonist (RS)-3,5-dihydroxyphenylglycine ((RS)-DHPG) increased the burst frequency up to 300% at concentrations of 50 to 100 microM, while it decreased the burst duration below 100 ms. In slices of subtype I mGluR1 or subtype I mGluR5 knockout mice, bicuculline elicited spontaneous epileptiform bursts with similar duration and frequency as those measured in wild-type mice but without the previous effects seen following application of DHPG at concentrations up to 100 microM. Likewise, in slices of wild-type mice, preincubation with mGluR1 antagonist, 1-aminoindan-1,5-dicarboxylic acid (AIDA) or mGluR5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP) blocked in both cases completely the increase in frequency following DHPG application. These findings suggest an interactive mechanism between mGluR1 and mGluR5 receptors in the modulation of epileptiform bursting activity by DHPG that could indicate a common intracellular signaling mechanism or possibly direct interaction between these two receptors.
Stoop
R
R
Institute of Cellular Biology and Morphology, University of Lausanne, Rue du Bugnon 9, CH-1005 Lausanne, Switzerland. rstoop@ibcm.unil.ch
Conquet
F
F
Pralong
E
E
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000145:classification / Q000235:genetics / Q000502:physiology*
C095756:1-aminoindan-1,5-dicarboxylic acid; C110735:3,5-dicarboxyphenylglycine; D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; C578936:Grm5 protein, mouse; D007189:Indans; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C121465:6-methyl-2-(phenylethynyl)pyridine; D005998:Glycine; D001640:Bicuculline