Stimulation of 22Na+ efflux from rat forebrain membrane vesicles by L-glutamic acid, L-aspartic acid and kainic acid.
A glass fiber filter assay method is described for measuring 22Na+ efflux stimulated by L-glutamic acid, L-aspartic acid and kainic acid from osmotically sensitive membrane vesicles prepared from rat brain. L-Glutamic acid and L-aspartic acid showed the greatest efficacy for the stimulation of 22Na+ efflux with EC50 values of 3 microM. Kainic acid produced 28% of the maximal efflux seen with L-glutamic acid or L-aspartic acid with an EC50 value of 1.5 microM. Quisqualic acid never showed statistically significant increases in 22Na+ efflux over control experiments. N-Methyl-D-aspartic acid showed no detectable efflux activity in this preparation. DL-2-Amino-4-phosphonobutyric acid (APB) inhibited up to 40% of the 50 microM L-glutamic acid-stimulated or 50 microM L-aspartic acid-stimulated 22Na+ efflux with an IC50 value of 1.5 nM. Calcium was required for the inhibitory action of APB, but not for the stimulatory actions of L-glutamic, L-aspartic, or kainic acids. L-Glutamic, L-aspartic, and kainic acids at concentrations above 100 microM were found to inhibit rather than to stimulate 22Na+ efflux. Veratridine (1 microM) had no influence on the 22Na+ efflux component which was produced by L-glutamic or kainic acids. We are unable to firmly establish the mechanism for the stimulated 22Na+ efflux.
Matthews
J C
JC
Department of Pharmacology, School of Pharmacy, University of Mississippi 38677.
Hsu
C H
CH
Morris
K R
KR
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism*; D013696:Temperature; D014701:Veratridine / Q000494:pharmacology
D005971:Glutamates; D001224:Aspartic Acid; D018698:Glutamic Acid; D014701:Veratridine; D012964:Sodium; D007608:Kainic Acid