Excessive release of [3H]noradrenaline and glutamate in response to simulation of ischemic conditions in rat spinal cord slice preparation: effect of NMDA and AMPA receptor antagonists.

Abstract

In the present study we investigated the effects of NMDA and non-NMDA glutamate receptor antagonists on the ischemia-evoked release of [3H]noradrenaline from rat spinal cord slices. An in vitro ischemia model (oxygen and glucose deprivation) was used to simulate the ischemic conditions known to cause neuronal injury. Spinal cord slices were loaded with [3H]noradrenaline and superfused with Krebs solution in a micro-organ bath. Both axonal stimulation and ischemia increased the release of [3H]noradrenaline, but the release in response to glucose and oxygen deprivation was [Ca2+]o independent. Dizocilpine (MK-801), an NMDA receptor antagonist, suppressed the release of [3H]noradrenaline produced by ischemia, while it enhanced the release of [3H]noradrenaline evoked by electrical field stimulation. In contrast, LY300168 (GYKI-53655) [(+/-)-3-N-methylcarbamyde-1-(4-aminophenyl)-4-methyl-1.8-methylen e-dioxy-5H-2.3-benzodiazepine] and its (-)isomer LY303070 (GYKI-53784) [(-)-3-N-methylcarbamyde-1-(4-aminophenyl)-4-methyl-1.8-methylene- dioxy-5H-2.3-benzodiazepine] AMPA receptor antagonists, had no effect on the release of [3H]noradrenaline evoked by either electrical stimulation or ischemia. Desipramine, a noradrenaline uptake inhibitor, potentiated the release of [3H]noradrenaline evoked by ischemia, while in the absence of [Ca2+]o but under conditions when [3H]noradrenaline release was further increased, it reduced the release. Dizocilpine also decreased glutamate and aspartate release, measured by high performance liquid chromatography, during ischemia. It is concluded that glutamate release and NMDA receptors, but not AMPA receptors, are involved in the acute effect of oxygen and glucose deprivation on the excessive release of noradrenaline and that this release is not related to physiological axonal conduction.

• Authors: T Nakai, E Milusheva, M Baranyi, Y Uchihashi, T Satoh, E S Vizi
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 366 Issue 2-3 Pg. 143-50 (Feb 05 1999) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10082194 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Antagonists
• Receptors, AMPA
• Receptors, N-Methyl-D-Aspartate
• Tritium
• Benzodiazepines
• GYKI 53655
• Glutamic Acid
• Dizocilpine Maleate
• Glucose
• Norepinephrine

Topics

• Animals
• Benzodiazepines (chemistry, pharmacology)
• Dizocilpine Maleate (pharmacology)
• Dose-Response Relationship, Drug
• Electric Stimulation
• Excitatory Amino Acid Antagonists (pharmacology)
• Glucose (pharmacology)
• Glutamic Acid (drug effects, metabolism)
• Hypoxia (physiopathology)
• In Vitro Techniques
• Ischemia (physiopathology)
• Male
• Norepinephrine (metabolism)
• Rats
• Rats, Wistar
• Receptors, AMPA (antagonists & inhibitors)
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)
• Spinal Cord (blood supply, drug effects, metabolism)
• Stereoisomerism
• Tritium