Kinetic cooperative effect of glycine receptor agonists and antagonists on the dissociation of strychnine binding.

The dissociation of [3H]strychnine binding was studied in synaptosomal membranes of rat spinal cord. Dissociation elicited by 100-fold dilution was accelerated by completely displacing concentrations of glycinergic agents. The rank order of acceleration was iso-THAZ < strychnine approximately taurine < R 5135 < avermectin b1a approximately beta-alanine << glycine (THAZ, 5,6,7,8-tetrahydro-4H-isoxazolo-(3,4-d)azepin-3-ol). The accelerating effects were correlated with the changes of entropy (r = 0.93) but not with the changes of free energies (r = 0.06) of their binding. Half-maximal acceleration was elicited by 58 microM glycine. The accelerating effects of glycine and beta-alanine were attenuated by the antagonists.