The glutamate analogue alpha-aminoadipic acid is taken up by astrocytes before exerting its gliotoxic effect in vitro.
DL- and L-alpha-aminoadipic acid (alpha-AA) are specific gliotoxins in vitro (Huck, S., F. Grass, and M. E. Hatten (1984) Neuroscience 12: 783-796). By combining immunohistochemical and autoradiographic techniques, we now show that DL-[14C]-alpha-AA is accumulated almost selectively by astrocytes in cultures of the dissociated postnatal mouse cerebellum, presumptive neurons being free of the radiolabel. High pressure liquid chromatography analysis of cultures incubated with D- or L-alpha-AA and DL-[14C]-alpha-AA autoradiograms conducted in the presence of D- or L-alpha-AA reveal a stereospecificity of astroglial L-alpha-AA uptake. Both the uptake of alpha-AA by astrocytes and alpha-AA-induced gliotoxicity were sodium dependent. Since 2 microM tetrodotoxin did not prevent the morphological changes, we conclude that sodium plays its role in alpha-AA-induced gliotoxicity by mediating the transport of the substance. Thus, alpha-AA appears to be taken up by the astrocytes before exerting its cytotoxic effect.
D015074:2-Aminoadipic Acid / Q000378:metabolism* / Q000633:toxicity; D000600:Amino Acids, Dicarboxylic / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001345:Autoradiography; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D002794:Choline / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003470:Culture Media; D051379:Mice; D008815:Mice, Inbred Strains; D009457:Neuroglia / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology
D000600:Amino Acids, Dicarboxylic; D003470:Culture Media; D015074:2-Aminoadipic Acid; D012964:Sodium; D002794:Choline