The Inhibitory Glycine Receptor A Candidate Protein of Signal Transduction in Neuroendocrine Tissue' zyx CORD-MICHAEL BECKER, CLAUDIA KLING, CORNEL MULHARDT, BRIGITTA SAUL, MA'ITHIAS HERKERT, AND JOCHEN KUHSEb zyx Zentrum f i r Molekulare Biologie and Neurologische Klinik Universitat Heidelberg Im Neuenheimer Feld 282 0-69120 Heidelberg, Germany bMax-Planck-Institut fur Hirnforschung Deutschordenstrajle 46 0-60528 FrankfurtlMain, Germany INTRODUCTION The physiological function of the central nervous system (CNS) depends on a balance of excitatory and inhibitory neuronal impulses. Although GABA serves as a major inhibitory neurotransmitter in cortex and cerebellum, glycine is the principal inhibitory transmitter in the lower parts of the CNS, where it is involved in the segmental regulation of spinal motoneurons by small inter-neurons, including the Renshaw cells.' Thus, glycine is present at high levels in the anterior horn of the grey matter,* and immunodetection has permitted a detailed analysis of its cellular and subcellular distribution. These studies show that glycine is enriched in terminals of spinal cord interneurons, whereas cholinergic motoneurons are immunonegative. In addition, the presence of glycine has been demonstrated in brain stem nuclei, in- cluding auditory and vestibular center^.^.^ Upon its release by the presynaptic terminal, glycine binds to postsynaptic receptors located on the neuronal surface. Binding of glycine to its receptor induces the opening of an intrinsic anion channel, resulting in chloride currents and a postsynaptic hyperp~larization.~ Receptor binding of glycine is competitively an- tagonized by the plant alkaloid strychnine. Consistent with the physiology of gly- cinergic synapses, sublethal strychnine poisoning causes motor disturbances, for example, hyperreflexia and increases in muscle tonus. Further symptoms of strych- nine intoxication include impairment of sensory, visual, and acoustic perception. Higher doses of strychnine lead to convulsions and death.6 ISOFORMS OF THE INHIBITORY GLYCINE RECEPTOR During postnatal development, two types of glycine receptor proteins are se- quentially expressed in rodent spinal cord. A neonatal isoform of the glycine receptor (Gly R,) prevails in newborn rodents, which is replaced by the adult-type receptor "This work was supported by Deutsche Forschungsgemeinschaft (SFB 317 and Heisenberg- Programm) and, zyxwvut in part, by the Hermann-und Lilly-Schilling-Foundation. zyx 155