Gamma-D-glutamylglycine and cis-2,3-piperidine dicarboxylate as antagonists of excitatory amino acids in the hippocampus.
The actions of gamma-D-glutamylglycine (DGG) and cis-2,3-piperidine dicarboxylate (PDA) were studied in thin hippocampal sections of the guinea pig by intracellular recording. DGG and PDA suppressed depolarizations induced in CA3 neurons by short pulses of L-aspartate (Asp), D-homocysteate (DH) or L-glutamate (Glu). Asp- and DH-responses were more susceptible to the antagonists than were Glu-responses. The sensitivity difference between Glu-responses and Asp- or DH-responses was not so pronounced that these antagonists could be used to differentiate between Glu-mediated and Asp-mediated synapses. Glu and Asp pulses induced long hyperpolarizing deflections in some neurons. In about half of these neurons, PDA and DGG were without effect on the hyperpolarizing responses. The depolarizing action of gamma-amino butyric acid was unaffected by DGG and PDA. These antagonists blocked excitatory postsynaptic potentials induced by fimbrial stimulation. These results suggest that DGG and PDA are relatively specific antagonists of excitatory amino acids in the hippocampus, and that Glu (or Asp) is the neurotransmitter released from axons of CA3 neurons.
D000596:Amino Acids / Q000037:antagonists & inhibitors*; D000818:Animals; D001224:Aspartic Acid / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004151:Dipeptides / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D006168:Guinea Pigs; D006710:Homocysteine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D010875:Pipecolic Acids / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000596:Amino Acids; D004151:Dipeptides; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D010875:Pipecolic Acids; D006710:Homocysteine; C007956:homocysteic acid; C028929:gamma-glutamylglycine; D001224:Aspartic Acid; D018698:Glutamic Acid; C029262:2,3-piperidinedicarboxylic acid