L-CCG-I activates group III metabotropic glutamate receptors in the hippocampal CA3 region.
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.
Kirschstein
Timo
T
Department of Epileptology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. timo.kirschstein@gmx.net
von der Brelie
Christian
C
Steinhäuser
Marius
M
Vinçon
Alisa
A
Beck
Heinz
H
Dietrich
Dirk
D
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
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