Stimulation of inositol phospholipid hydrolysis by excitatory amino acids is enhanced in brain slices from vulnerable regions after transient global ischemia.
Stimulation of inositol phospholipid hydrolysis by transmitter receptor agonists was measured in slices from hippocampus, cerebral cortex, and corpus striatum at various intervals after transient global ischemia in rats. Ischemia was induced through the four-vessel occlusion model. Stimulation of [3H]inositol monophosphate formation by excitatory amino acids was greatly enhanced in hippocampal slices prepared from ischemic rats at 24 h or 7 days after reperfusion. This potentiation was more evident using ibotenic acid and was also observed in cerebral cortex, but not in corpus striatum. This regional profile correlated with the pattern of ischemia-induced neuronal damage observed under our experimental conditions. The enhanced responsiveness to excitatory amino acids was always accompanied by an increase in both basal and norepinephrine-stimulated [3H]inositol monophosphate formation. In contrast, stimulation of [3H]inositol monophosphate formation by carbamylcholine was not modified in hippocampal or cortical slices from ischemic animals.
Seren
M S
MS
Fidia Research Laboratories, Abano Terme, Italy.
Aldinio
C
C
Zanoni
R
R
Leon
A
A
Nicoletti
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000378:metabolism; D006868:Hydrolysis; D007051:Ibotenic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D015424:Reperfusion
D005971:Glutamates; D007295:Inositol Phosphates; D010069:Oxadiazoles; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016318:Quisqualic Acid; D002217:Carbachol; D009638:Norepinephrine