MCPG antagonizes metabotropic glutamate receptors but not long-term potentiation in the hippocampus.
In the CA1 and CA3 regions of the guinea pig hippocampus, we have tested the ability of the new antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) to inhibit the well-known effects of (trans)-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), a specific agonist of glutamate metabotropic receptors. Whole-cell recordings showed that MCPG was able to antagonize the blocking action of ACPD on IAHP in the CA1 region. In addition, we report here that MCPG also antagonized the presynaptic inhibitory actions of ACPD on field excitatory postsynaptic potentials in both areas CA1 and CA3. Thus, MCPG proved to be an effective tool for determining physiological roles of the glutamate metabotropic receptors in synaptic transmission in the hippocampus. We next tested the possible effects of this antagonist on long-term potentiation (LTP). In completely blind experiments MCPG was without effect on LTP in both areas CA1 and CA3. In conclusion, our results suggest that, although MCPG is a valuable antagonist of the ACPD-sensitive receptors, it has no inhibitory effect on LTP.
Department of Pharmacology, University of California at San Francisco 94143-0450.
O J
OJ
Manzoni
M G
MG
Weisskopf
R A
RA
Nicoll
D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D001565:Benzoates; D009498:Neurotoxins; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; C079694:alpha-methyl-4-carboxyphenylglycine; D005998:Glycine