Kainate-enhanced release of D-[3H]aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital.
A study was made of the actions of the excitant neurotoxin, kainic acid, on the uptake and the release of D-[2,3-3H]aspartate (D-ASP) in slices of guinea pig cerebral neocortex and striatum. The slices took up D-ASP, reaching concentrations of the amino acid in the tissue which were 14-23 times that in the medium. Subsequently, electrical stimulation of the slices evoked a Ca2+-dependent release of a portion of the D-ASP. Kainic acid (10(-5)-10(-3) M) produced a dose-dependent inhibition of D-ASP uptake. The electrically evoked release of D-ASP was increased 1.6-2.0 fold by 10(-5) and 10(-4)M kainic acid. The kainate-enlarged release was Ca2+-dependent. Dihydrokainic acid, an analogue of kainic acid with little excitatory or toxic action, did not increase D-ASP release but depressed D-ASP uptake. Attempts were made to block the action of kainic acid with baclofen and pentobarbital, compounds which depress the electrically evoked release of L-glutamate (L-GLU) and L-aspartate (L-ASP). Baclofen (4 X 10(-6)M), an antispastic drug, and pentobarbital (10(-4)M), an anesthetic agent, each inhibited the electrically evoked release of D-ASP and prevented the enhancement of the release above control levels usually produced by 10(-4)M kainic acid. It is proposed that 10(-5) and 10(-4)M kainic acid may enhance the synaptic release of L-GLU and L-ASP from neurons which use these amino acids as transmitters. This action is prevented by baclofen and pentobarbital. In view of the possibility that cell death in Huntington's disease could involve excessive depolarization of striatal and other cells by glutamate, baclofen might be effective in delaying the loss of neurons associated with this condition.
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001418:Baclofen / Q000494:pharmacology*; D001692:Biological Transport; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006168:Guinea Pigs; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D010634:Phenobarbital / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011759:Pyrrolidines; D014316:Tritium; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D001418:Baclofen; D005947:Glucose; D007608:Kainic Acid; D010634:Phenobarbital