J Korean Neurol Assoc.  1997 Oct;15(5):964-973.

Mechanisms of release of [3H] Hydroxytryptamine evoked by hypoxia and hypoglycemia in rat cerebral cortex slices

• Song DW
• Kim YH
• Kim KW

Abstract

Pathophysiology of brain ischemia is characterixed by a complex cascade of hemodynamic, electrophysiological and biochemical processes. It has been generally accepted that glutamate mediates the ischemic brain damage, excitotoxicity, and induce neurotramsmitter release from various brain tissues in ischemic milieu. In presen study, the mechanism for ischemia-induced [3HT]5-hydroxytryptamine(5-HT) from cerebral cortex slices of the rat was examined. Ischemia, deprivation of oxygen and glucose from Mg2+-free artificl cerebrospinal fluid, induced significiant release of [3H]5-HT(7.2+0.6% of total tissue content) from the tissues. This ischemia-induced release of [3H]5-HT from the slices was significiantly attenuated by TTX(1 yM), Mg2+(102mM). MK-801(10yM), ketamine(10yM), NMDA receptor antagonists, DNQX(30yM), a kainate/AMPA receptor antagonist, or carbetapentane(31yM), an inhibitor of glutamate release. Fluoxetine, a selective blocker for 5-HT transporter, inhibited the ischemia-induced release of [3H]5-HT. Omission of Ca2+ from incubation media potentiated ischemia-evoked [3H]5-HT release and the inhibitory effect of blockers for transporter. Dantrolene (30yM) and ryanodine(100 nM) and -conotoxinGVIA(100 nM), inhibitors of N-type Ca2+ channels, sifnificiantly attenuated the ischemia-induced release of [3H]5-HT, but verapamil(5 yM), an inhibitor of L-type Ca2+ channels, did not. Fluoxetine(100 nM), a relatively selective 5-HT transporter blocker, significiantly inhibited the ischemia-induced release of [3H]5-HT. Theses results suggest that glutamate is involned in ischemia-evoked [3H]5-HT release, and this release is achieved by Ca2+=dependent exocytosis and reverdsal of transporters, and can be modulated by various neuronal mechanisms.

Keyword

Rat Cerebral Cortex Slices; Ischemia; [3H]5-HT; Release

MeSH Terms

Animals
Anoxia*
Biochemical Processes
Brain
Brain Ischemia
Cerebral Cortex*
Cerebrospinal Fluid
Dantrolene
Exocytosis
Fluoxetine
Glucose
Glutamic Acid
Hemodynamics
Hypoglycemia*
Ischemia
N-Methylaspartate
Neurons
Oxygen
Rats*
Serotonin*
Dantrolene
Fluoxetine
Glucose
Glutamic Acid
N-Methylaspartate
Oxygen
Serotonin