Kainic acid evoked release of D-[3H]aspartate from rat striatum in vitro: characterization and pharmacological modulation.
A presynaptic stimulatory action of kainic acid (KA) on the release of glutamate from corticostriatal neurons is thought to contribute to the toxic effect of KA on cell bodies of neurons in the striatum. To characterize the action of KA on the presynaptic amino acid release, its effect was evaluated on the spontaneous efflux of D-[3H]aspartate (D-[3H]Asp), a marker for glutamatergic neurons, from slices of rat striatum in superfusion experiments. In the concentration range 0.5-10.0 mM, KA significantly increased the spontaneous efflux of D-[3H]Asp. Under similar conditions potassium (K+, 25 mM), veratridine, D-aspartic acid (D-Asp), and N-methyl-D-L-aspartic acid (NMDLA) also induced the efflux of the radiolabelled amino acid. The stimulatory effect of KA, like that of K+, was partly calcium dependent. The action of veratridine, D-Asp, and NMDA was not calcium dependent. Tetrodotoxin (TTX) blocked the action of veratridine on D-[3H]Asp efflux but did not affect the action of KA. In a sodium-free perfusion medium the action of KA was greatly reduced. Dihydrokainic acid produced an effect on D-[3H]Asp efflux comparable in magnitude with that produced by KA. The latter, at a dose of 5 mM, also stimulated the efflux of D-[3H]Asp from the cortex, hippocampus and the septum but its effect on these regions was weaker than its striatal effect. The action of several agents, which previously have been found to depress transmitter release in other systems and (or) to modify the neurotoxic action of KA in vivo, was evaluated on the KA-evoked D-[3H]Asp efflux from striatal slices.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology / Q000633:toxicity*; D011188:Potassium / Q000494:pharmacology; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000502:physiology; D014316:Tritium
D011759:Pyrrolidines; D014316:Tritium; D001224:Aspartic Acid; D001971:Bromocriptine; C020889:dihydrokainic acid; D012964:Sodium; D011188:Potassium; D007608:Kainic Acid; D002118:Calcium