Magnesium ions inhibit the stimulation of inositol phospholipid hydrolysis by endogenous excitatory amino acids in primary cultures of cerebellar granule cells.
Omission of Mg2+ from the incubation buffer results in a six- to eightfold increase in [3H]inositol-1-phosphate ([3H]Ins-1-P) accumulation in primary cultures of cerebellar granule cells at 7-9 days in vitro. This increase is reversed by low concentrations of 2-amino-5-phosphono-valerate (APV), a result indicating that the absence of Mg2+ facilitates the activation of a specific receptor by the endogenous excitatory amino acids (presumably L-glutamate and L-aspartate) released from the granule cells. The absence of Mg2+ also potentiates the action of exogenously applied N-methyl-D-aspartate (NMDA), L-glutamate, L-aspartate, and kainate. In contrast, the action of quisqualate is virtually unaffected by Mg2+ and is resistant to APV inhibition. Addition of the depolarizing agent veratridine enhances the accumulation of [3H]Ins-1-P also in Mg2+-containing buffer. The action of veratridine is antagonized by APV, a result suggesting that, under depolarized conditions, the NMDA receptor can be activated by the endogenously released excitatory amino acids, despite the presence of Mg2+. Accordingly, in the presence of Mg2+, veratridine potentiates the action of exogenously applied NMDA but does not facilitate the action of quisqualate.
D015763:2-Amino-5-phosphonovalerate; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D004357:Drug Synergism; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000378:metabolism*; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D013403:Sugar Phosphates / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D000596:Amino Acids; D005971:Glutamates; D007295:Inositol Phosphates; D010069:Oxadiazoles; D013403:Sugar Phosphates; C002647:inositol 1-phosphate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D014701:Veratridine; D015763:2-Amino-5-phosphonovalerate; D016318:Quisqualic Acid; D014633:Valine; D008274:Magnesium; D007608:Kainic Acid