The inhibitory neurotransmitter glycine also plays an inportant role as coagonist at excitatory N-methyl-D-aspartate (NMDA)-type glutamate receptors. Despite high glycine concentrations in the cerebrospinal fluid and in nervous tissue, the amount of glycine that normally reaches NMDA receptors is reduced to subsaturating levels by perisynaptic glycine transporters. Ahmadi et al. show that in the dorsal horn of the spinal cord, synaptically released glycine enhances NMDA receptor-mediated currents. During high levels of neuronal activity, glycine released from glycinergic inhibitory interneurons can spill over and reach NMDA receptors at neighboring glutamatergic synapses. Blockade of this phenomenon by the neuropeptide nocistatin can selectively inhibit NMDA receptor-mediated excitation in the dorsal horn and could thus be used therapeutically to treat inflammatory pain.
S. Ahmadi, U. Muth-Selbach, A. Lauterbach, P. Lipfert, W. L. Neuhuber, H. U. Zeilhofer, Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine. Science 300, 2094-2097 (2003). [Abstract] [Full Text]