The glycine receptor: pharmacological studies and mathematical modeling of the allosteric interaction between the glycine- and strychnine-binding sites.
The displacement by glycine of 3H-strychnine binding to rat spinal cord membranes cannot be explained by a simple competitive interaction. Indeed, protein-modifying reagents can completely abolish the inhibition of 3H-strychnine binding by glycine and other agonists, whereas the interaction of strychnine itself and other related compounds with the binding site is unimpaired. Moreover, glycine cannot inhibit completely saturable 3H-strychnine binding, the extent of its maximum inhibitory effect depending on the ionic composition of the medium. Hill coefficients less than 1 (whose magnitude also depends on the assay medium) were obtained from glycine displacement curves. These properties are consistent with a mathematical model of two different, but mutually interacting, binding sites for strychnine and glycine on the glycine receptor. The effect of ions and protein-modifying reagents might be explained in this model as modifications of the mechanisms that mediate the allosteric interaction, and/or the affinity of glycine for the receptor. The agonists beta-alanine and taurine and the new antagonists, THAZ, iso-THAZ, and 4,5-TAZA, also seem to interact with a site different from the strychnine-binding site, probably the glycine-binding site.
D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D005998:Glycine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013331:Strychnine / Q000378:metabolism*
D018009:Receptors, Glycine; D017981:Receptors, Neurotransmitter; D013331:Strychnine; D005998:Glycine