Effects of alpha-keto-delta-guanidinovaleric acid on inhibitory amino acid responses on mouse neurons in cell culture.
The experimentally proven convulsant alpha-keto-delta-guanidinovaleric acid (alpha-K-delta-GVA) was applied to mouse spinal cord neurons in primary dissociated cell culture to assess its effects on postsynaptic gamma-aminobutyric acid (GABA)- and glycine (GLY)-responses. Intracellular microelectrode recording techniques were used. alpha-K-delta-GVA reversibly inhibited both GABA- and GLY-responses in a concentration-dependent manner. The effect of alpha-K-delta-GVA on GABA-responses was not antagonized by co-application of the benzodiazepine receptor antagonist CGS 9896. The results suggest that alpha-K-delta-GVA inhibited responses to the inhibitory neurotransmitters GABA and GLY by blocking the chloride channel. This action might underlie the convulsant effect of this compound in rabbit. The possible pathophysiological importance of alpha-K-delta-GVA in hyperargininemic patients is discussed.
De Deyn
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PP
Department of Neurology, University of Michigan Medical Center, Ann Arbor 48104.
Marescau
B
B
Macdonald
R L
RL
D000818:Animals; D002478:Cells, Cultured; D005333:Fetus; D005727:Ganglia, Spinal / Q000502:physiology; D005998:Glycine / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D006146:Guanidines; C022249:alpha-keto-delta-guanidinovaleric acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine