N-methyl-D-aspartate receptor-mediated increase in intracellular calcium is reduced by ketamine and phencyclidine.
L-Glutamate, N-methyl-D-aspartate, quisqualate and potassium chloride enhanced Ca2+ accumulation by rat cortical slices as determined using 45Ca2+ uptake and Ca2+ mobilisation in cortical synaptosomes as determined using quin-2 fluorescence. Quinolinate and kainate were ineffective. Responses to L-glutamate and N-methyl-D-aspartate were blocked by non-competitive (ketamine, phencyclidine, Mg2+) and competitive (2-amino-5-phosphonovalerate) antagonists. These data suggest that activation of excitatory amino acid receptors in the cortex results in enhanced Ca2+ mobilisation which can be blocked by selective antagonists. Such effects may be related to neurotoxic properties of the excitatory amino acids and the neuroprotection afforded by excitatory amino acid antagonists.
O'Shaughnessy
C T
CT
Department of Physiology, Royal Veterinary College, London, U.K.
Lodge
D
D
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D007649:Ketamine; D010622:Phencyclidine; D002118:Calcium