Picolinic acid modulates kainic acid-evoked glutamate release from the striatum in vitro.
Since picolinic acid, a tryptophan metabolite yielded by the kynurenine pathway, selectively attenuates quinolinic and kainic acid excitotoxicity that is dependent on the presence of a glutamatergic afferent input, it was hypothesized that this agent may inhibit the presynaptic release of glutamate. Using superfused rat striatal slices, this study examined the potential of picolinic acid, and related pyridine monocarboxylic acids, to modify kainic acid-induced glutamate release. Kainic acid (0.25, 0.5 and 1.0 mM) stimulated the release of glutamate, an effect which was calcium dependent and was attenuated in the presence of the kainate/AMPA receptor antagonist, 6,7-dinitroquinoxalene-2,3-dione (500 microM). Picolinic acid significantly decreased glutamic acid release evoked by exposure of striatal slices to 1 mM kainate in the presence of calcium. The inhibitory action of picolinic acid on kainate-induced release was also shared by nicotinic and isonicotinic acid. In the absence of external calcium, kainic acid-induced glutamate release was significantly reduced by approximately 65%. Under this condition, picolinic acid (100 microM) failed to influence kainic acid-induced release. Picolinic acid (100 microM) itself increased glutamate release by 35% over basal release. While the ability of picolinic acid to inhibit excitotoxin-induced release supports the notion that it may act presynaptically to modify excitotoxicity, lack of structural specificity in its action tends to cast doubt on this mechanism of action.
Vrooman
L
L
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
Jhamandas
K
K
Boegman
R J
RJ
Beninger
R J
RJ
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000037:antagonists & inhibitors*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010848:Picolinic Acids / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D005971:Glutamates; D018377:Neurotransmitter Agents; D010848:Picolinic Acids; D011810:Quinoxalines; D018698:Glutamic Acid; C056723:FG 9041; C030614:picolinic acid; D007608:Kainic Acid