Rapid increase of intracellular Ca2+ concentration caused by aminoadipic acid enantiomers in retinal Müller cells and neurons in vitro.

The ability of the gliotoxic compounds D,L-, D- or L-2-aminoadipic acid (AAA) to increase selectively the intracellular concentration of free calcium ion ([Ca2+]i) was examined in Müller cells cultured with or without retinal neurons. The monitoring of [Ca2+]i following exposure to 0.06 to 6 mM AAA was performed by a microfluorometry using a fluorescent Ca2+ indicator, Fura-2 acetoxymethyl ester. A rapid increase of [Ca2+]i occurred in the Müller cells following exposure to a relatively low concentration of the L-isomer. This is compatible with the known strong gliotoxicity of this isomer. The D,L- and D-forms of AAA activated neurons at low concentrations and activated the Müller cells at higher concentrations. The D-isomer appears to act selectively on retinal neurons and may be an agonist of an excitatory amino acid receptor. These results indicate that the ability of AAA to elevate cytosolic [Ca2+]i depends on the stereospecificity of the AAA and on cell type.