Effects of baclofen on amino acid release.
This study showed the effects of baclofen on endogenous excitatory (Glu and Asp) and non-excitatory (Tau, Gly and Ala) amino acid release. (A) Release was stimulated by K+ 30 mM in rat frontal cortex slices in vitro (evoked release in ng/g tissue per 5 min): 3739 +/- 215 (Asp), 3429 +/- 357 (Glu), 763 +/- 181 (Tau), 945 +/- 71 (Ala), 468 +/- 44 (Gly). (B) Release was largely Ca(2+)-dependent for all amino acids but Ca(2+)-independent release was observed for Asp and Glu (29 and 32%, of total evoked release respectively). (C) Ca(2+)-dependent release was inhibited by baclofen 100 microM (% of inhibition taking as 100%, the Ca(2+)-dependent release in the absence of baclofen): 46 (Asp), 96 (Glu) (85% inhibition by baclofen 10 microM), 100 (Tau), 77 (Ala). Ca(2+)-independent release was inhibited: 87 and 88% (Asp), 85 and 95% (Glu) by baclofen 10 and 100 microM respectively. It is concluded that baclofen at a high concentration inhibits the evoked release of Glu, Asp, Tau and Ala due to inhibition of the Ca(2+)-dependent fraction and also of the Ca(2+)-independent component in the case of Glu and Asp. Baclofen at a low concentration inhibits only Glu- and Asp-evoked release (total release) due to inhibition of both Ca(2+)-dependent and -independent fractions in the case of Glu and to inhibition of the Ca(2+)-independent fraction in the case of Asp. The possibility that baclofen might affect the Ca(2+)-independent carrier-mediated release of Glu-Asp is discussed.
Losada
M E
ME
Instituto de Investigaciones Farmacológicas (ININFA), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Acosta
G B
GB
D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D001418:Baclofen / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D005973:Glutamine / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D013654:Taurine / Q000378:metabolism
D000596:Amino Acids; D005973:Glutamine; D013654:Taurine; D001216:Asparagine; D001418:Baclofen; D000409:Alanine; D011188:Potassium; D002118:Calcium; D005998:Glycine