Neuropharmacology
-
The neurotransmitter glycine is removed from the synaptic cleft by two Na(+)-and Cl(-)-dependent transporters: GLYT1 and GLYT2. GLYT1, expressed in glial processes of glycinergic areas and in glia and neurons of glutamatergic pathways that contain N-methyl-d-aspartate (NMDA) receptors, is essential for regulating glycine levels both at glycinergic and NMDA-containing synapses. GLYT2 is the transporter present in glycinergic neurons and provides cytosolic glycine for vesicular release from glycinergic terminals. ⋯ Opposite chimeras containing TM1 or TM3 of GLYT1 on GLYT2 structure became sensitive to NFPS. Individual substitution mutants of GLYT2 TM1 residues on GLYT1 and opposite GLYT1 TM1 residues on GLYT2 indicate that the more N-terminal portion of GLYT1 including residue E40 contributes to NFPS specificity. Our results demonstrate that TM1 and TM3, but not TM2, contain residues involved in the specific action of NFPS on GLYT1.