Glycine receptor mechanisms

Glycine receptor function is modulated by alcohols and anesthetics [4]. Amino acid residue al(S267) is critical for alcohol potentiation, as mutation to small residues (Gly, Ala) enhance, and mutation to large residues (His, Cys, Tyr) diminish the ethanol effect. Glycine recqrtor modulation by Zn2+ involves structural determinants located within the large N-terminal domain. Additional glycinergic modulators include neuroactive steroids and the anthelmintic, ivermectin, which activates glycine receptors by a novel, strychnine-insensitive mechanism. 

S. Daniels (2003). General anesthetic effects on glycine receptors. In J. Antognini, E. Carstens, D. Raines (Eds.). Neural Mechanisms of Anesthesia. Totowa, New Jersey Humana Press, pp. 333-344. 

Walstrom, K.M. et al. (1994) Mechanism for the channel-opening reaction of strychnine-sensitive glycine receptors on cultured embryonic mouse spinal cord ceils. Biochemistry. 33,7718-7730. 

Pharmacology and Mechanism of Action. Felbamate appears to act as an antagonist of the glycine receptor site on the V-methyl-D-aspartate (NMDA) receptor. This action inhibits the initiation and propagation of seizures. It also may inhibit NMDA/glycine-stimnlated increases in intracellular Ca . ... 

At the same time, several other mechanisms may be activated to compensate for some of the excitatory effect, perhaps to keep the system from being hyperreactive. These mechanisms include (1) presynaptic inhibition of glutamate release from the primary afferent terminals, (2) activation of the NKl receptors on the soma/dendrite of GABAergic intemeurons to enhance GABA release, and (3) an enhanced glycine synaptic transmission via an enhanced glycine receptor function through a protein kinase C or a Ca/calmodulin dependent protein kinase 11 pathway (Fig. 2). 

The other important molecular target of ethanol is the N-methyl-D-apartate receptor (NMDA-R), which is acutely inhibited although the mechanism is not clear. It was speculated that at least in some brain region the coactivating glycine sites are involved and/or the coactivating polyamine sites. The receptors containing... 

The NMDA receptor is an ionotropic glutamate receptor involved in fast excitatory neurotransmission. It plays a key role in a variety of CNS functions, most notably long-term potentiation (LTP) and neuronal plasticity, and is regulated by several mechanisms. One such mechanism involves the amino acid glycine (1). 

Kerchner, G. A., Wang, G. D., Qiu, C. S., Huettner, J. E., and Zhuo, M. (2001) Direct presynaptic regulation of GABA/glycine release by kainate receptors in the dorsal horn an ionotropic mechanism. Neuron 32,477—488. 

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