title: L-CCG-I activates group III metabotropic glutamate receptors in the hippocampal CA3 region.
abstract: Specific agonists of metabotropic glutamate receptors (mGluRs) provide powerful tools to discriminate afferent fibers originating from different presynaptic neurons. The group II mGluR agonists L-CCG-I ((2S,1'S,2'S)-2-(2-carboxycyclopropyl)glycine) and DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxy-cyclopropyl)glycine) are commonly used to distinguish between mossy fiber and associational-commissural (A/C) fiber input to the hippocampal CA3 region because only on the former group II mGluRs are expressed. Since previous reports indicated that L-CCG-I can activate group III mGluRs as well, we investigated whether L-CCG-I depresses A/C field potentials. L-CCG-I (10-300 microM) exhibited a significant dose-dependent and reversible reduction of A/C field potentials by 8 +/- 4% (10 microM), by 32 +/- 4% (100 microM, p < 0.001) and by 38 +/- 7% (300 microM, p < 0.05) that was accompanied by a concomitant increase in paired-pulse facilitation. Moreover, the selective group III antagonist (R,S)-alpha-methylserine-O-phosphate (MSOP; 100 microM) significantly reduced the field potential inhibition by L-CCG-I (100 microM) to 9 +/- 4% (p < 0.05). In contrast, DCG-IV did not affect A/C field potentials. In conclusion, the purported group II mGluR agonist L-CCG-I depresses A/C synaptic transmission by activation of group III mGluRs. For this reason, DCG-IV should be the drug of choice when aiming to discriminate between mossy fiber and A/C input to CA3 pyramidal cells.
authors.affiliation: Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. timo.kirschstein@gmx.net
authors.forename: Timo
authors.initials: T
authors.lastname: Kirschstein
authors.forename: Christian
authors.initials: C
authors.lastname: von der Brelie
authors.forename: Marius
authors.initials: M
authors.lastname: Steinhäuser
authors.forename: Alisa
authors.initials: A
authors.lastname: Vinçon
authors.forename: Heinz
authors.initials: H
authors.lastname: Beck
authors.forename: Dirk
authors.initials: D
authors.lastname: Dietrich
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000494:pharmacology*; D000818:Animals; D003521:Cyclopropanes / Q000494:pharmacology; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008024:Ligands; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D010768:Phosphoserine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000600:Amino Acids, Dicarboxylic; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; C120877:methylserine phosphate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D010768:Phosphoserine; C035261:(alpha-carboxycyclopropyl)glycine; D005998:Glycine