Presynaptic inhibitory action of the group II metabotropic glutamate receptor agonists, LY354740 and DCG-IV.
Electrophysiological studies were carried out on the presynaptic inhibitory action of the group II metabotropic glutamate (mGlu) receptor agonists (+)-2-aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) and (2S,1'R,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) in three paths of the rat hippocampus, the medial and lateral perforant path to the dentate gyrus, and the Schaffer collateral/commissural path to CA1. LY354740 caused a dose-dependent reversible inhibition of the field excitatory postsynaptic potential (EPSP) in the medial and lateral perforant paths, with an EC50 of 115 +/- 16 nM and 230 +/- 58 nM, respectively. Maximal inhibition by LY354740 was much greater in the medial path (about 80%) than in the lateral path (about 50%). No inhibition was observed in CA1. A presynaptic inhibition was confirmed by LY354740 inducing dose-dependent changes in paired-pulse depression/facilitation. DCG-IV had a similar action to LY354740, but with a lower potency.
Department of Physiology, Trinity College, Dublin, Ireland.
J
J
Kilbride
L Q
LQ
Huang
M J
MJ
Rowan
R
R
Anwyl
D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D001643:Bridged Bicyclo Compounds; D003521:Cyclopropanes; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; C104753:eglumetad; D005998:Glycine