Influence of NMDA Receptor Antagonists on Glycine Receptor Isoform Expression in Spinal Cord Cultures
The physiology of the amino acid transmitter glycine is well characterized in spinal cord, where it is involved in both mutual and feedback inhibition by recurrent axon collaterals of spinal motoneurons. Glycinergic inhibition is mediated by small interneurons within the spinal gray matter, including the Renshaw cells (Aprison and Daly 1978). Upon its release by the inhibitory neuron, glycine binds to postsynaptic receptors where it causes an intrinsic chloride channel to open. The resulting chloride influx produces a postsynaptic hyperpolarization and drastically decreases neuronal firing (Bormann et al. 1987). Glycinergic inhibition is also found in spinal nociceptive, brain stem auditory, and other CNS systems as well as in the retina (reviewed by Becker 1992). The convulsant alkaloid strychnine competitively antagonizes receptor binding of glycine, and, conversely, glycinedisplaceable [3H]strychnine binding has been established as a pharmacological probe of inhibitory glycine receptors. Heterogeneity is a widespread phenomenon of neurotransmitter receptors in the mammalian CNS (Betz 1990). Different isoforms have also been identified of the inhibitory glycine receptor (reviewed by Betz and Becker 1988; Langosch et al. 1990; Becker 1992). In contrast, high-affinity binding sites for [3H]glycine are distinct from inhibitory glycine receptors and are thought to reflect a regulatory domain of the N-methyl-D-aspartate (NMDA) receptor (Betz and Becker 1988; Monaghan et al. 1989; Moriyoshi et al. 1991).
KeywordsNMDA Receptor NMDA Receptor Antagonist Glycine Receptor Spinal Cord Neuron Mouse Spinal Cord
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