5-HT control of ischemia-evoked glutamate efflux from human cerebrocortical slices.
The aim of the present investigation was to explore if glutamate efflux from human cerebrocortical slices caused by oxygen/glucose deprivation can be controlled by 5-hydroxytryptamine (5-HT). Slices were superfused in aerobic conditions or in conditions simulating moderate ischemic insult (24 min oxygen and glucose deprivation) and the efflux of previously accumulated [3H]D-aspartate and of endogenous glutamate was measured in superfusate fractions. The efflux of both [3H]D-aspartate and endogenous glutamate evoked by ischemia were reduced by at least 50% in the presence of 5-HT (1 microM). Moreover, the 5-HT(1A) receptor agonist 8-OH-DPAT (1 microM) mimicked the 5-HT effect. We conclude that activation of 5-HT receptors of the 5-HT(1A) subtype might help to control glutamate efflux and excitotoxic damage during ischemia in human cerebral cortex and would deserve to be considered in a multipharmacological approach to neuroprotection in brain ischemia.
Marcoli
Manuela
M
Dipartimento di Medicina Sperimentale, Sezione di Farmacologia e Tossicologia, Università di Genova, Genoa, Italy.
Cervetto
Chiara
C
Castagnetta
Mauro
M
Sbaffi
Pierfilippo
P
Maura
Guido
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001224:Aspartic Acid / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000172:deficiency; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D002534:Hypoxia, Brain / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015427:Reperfusion Injury / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D017366:Serotonin Receptor Agonists; D001224:Aspartic Acid; D012701:Serotonin; D018698:Glutamic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D005947:Glucose