Activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices.
We have investigated the contribution of excitatory amino acid receptor activation to the inhibition of protein synthesis observed after anoxia in rat hippocampal slices. Protein synthesis was assessed in normoxic medium by measuring the incorporation of [14C]lysine into perchloric acid-insoluble tissue extracts. Protein synthesis was impaired after anoxia; the extent of inhibition was dependent on the duration of anoxia and on the time allowed for postanoxic recovery. There was a similar impairment under normoxic conditions when the N-methyl-D-aspartate (NMDA) receptor channel was activated by removing Mg2+ and adding NMDA. This was prevented by noncompetitive antagonists of the NMDA receptor channel (MK-801, phencyclidine, and N-allylnormetazocine). In contrast, incubation with the NMDA antagonists failed to prevent the protein synthesis inhibition caused by anoxia, although it moderately facilitated the postanoxic recovery. Protein synthesis was also impaired under normoxic conditions after incubation with quisqualate and kainate, agonists of non-NMDA glutamate receptors. This impairment was prevented by 6-cyano-7-nitroquinoxaline-2,3-dione, an antagonist of these receptors. Although 6-cyano-7-nitroquinoxaline-2,3-dione alone failed to prevent anoxic damage, when used in combination with an NMDA antagonist it did partially enhance the later recovery of protein synthesis. These results indicate that the activation of excitatory amino acid receptors cannot alone account for anoxia-induced impairment of protein synthesis in rat hippocampal slices.
Department of Pharmacology, Boehringer Ingelheim KG, F.R.G.
A J
AJ
Carter
R E
RE
Müller
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002250:Carbon Radioisotopes; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D007608:Kainic Acid / Q000494:pharmacology; D008239:Lysine / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology
D002250:Carbon Radioisotopes; D005971:Glutamates; D009419:Nerve Tissue Proteins; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D016318:Quisqualic Acid; D010620:Phenazocine; D010622:Phencyclidine; D008239:Lysine; D007608:Kainic Acid