Glutamat - Ein Transmitter im Spannungsfeld zwischen Toxin und Trophin

Zusammenfassung

Glutamat ist der wichtigste exzitatorische Neurotransmitter im Zentralnervensystem. Seine Wirkungsweise ist ebenso vielfältig wie es die molekularen Strukturen der durch Glutamat aktivierbaren Rezeptoren sind. Das glutamaterge System nimmt modulierenden Einfluss auf nahezu sämtliche Neurotransmittersysteme. Zudem spielt Glutamat in wichtigen zentralnervösen Prozessen wie der hippokampalen Langzeitpotenzierung, einem zellulären Modell für Lernen und Gedächtnis, und der zentralen Sensibilisierung für Schmerzreize im Hinterhorn des Rückenmarks eine zentrale Rolle, die insbesondere über den NMDA-Rezeptor vermittelt wird. Doch die Wirkung von Glutamat geht weit über seine Wirkung als exzitatorischer Neurotransmitter hinaus. So entfaltet Glutamat zumindest in bestimmten Entwicklungsphasen des Zentralnervensystems auch eine neurotrophische Wirkung. Die über den NMDA-Rezeptor vermittelte Exzitotoxizität von Glutamat ist als gemeinsame Endstrecke des akuten wie auch des chronischen Nervenzelluntergangs von entscheidender Bedeutung im Hinblick auf zahlreiche akute neurologische, neurodegenerative und neurometabolische Erkrankungen. Von einer Modulation des glutamatergen Systems z. B. durch Glutamatantagonisten erhofft man sich daher neuartige Therapien dieser pathogenetisch unterschiedlichen Erkrankungen.

Abstract

Glutamate is the most important excitatory transmitter in the central nervous system. A tremendous complexity in the actions of this excitatory transmitter was found and an equally great complexity in the molecular structures of the receptors activated by glutamate. The glutamate receptor system influences nearly all other neurotransmitter systems. Glutamate also plays a central role in important processes of the central nervous system like the long-term potentiation in the hippocampus and the central sensitization for pain stimuli in the spinal cord, which is predominantly mediated by NMDA-receptors. But there are actions of glutamate beyond its function as an excitatory transmitter. Glutamate also has a trophic influence on neurons - depending upon the developmental stage. The excitotoxicity of glutamate mediated by NMDA-receptors is the common ultimate mechanism of acute and chronical nerve cell death and plays an important role in many acute neurologic diseases. The modulation of the glutamate system for example by antagonist of the glutamate-receptors might be a possible way in therapy of many different diseases of the central nervous system.

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