title: Inhibition schemes for acetylcholine receptor-mediated ion translocation in the presence of various kinds of inhibitors.
abstract: Some basic inhibition schemes for acetylcholine receptor (AChR)-mediated ion translocation in the presence of agonist, cholinergic ligand, and inhibitors are proposed on the basis of the minimum reaction scheme (Hess, G.P., Cash, D.J., & Aoshima, H. (1983) Annu. Rev. Biophys. Bioeng. 12, 443-473). Equations for the rate coefficients of ion flux before and after desensitization, JA and JD, and for desensitization, a, were derived from each scheme, assuming that binding of inhibitors to AChR does not affect the values of rate and equilibrium constants of cholinergic ligand to the receptor. In the presence of inhibitors, AChR-mediated transmembrane Li+ influx caused by carbamylcholine (Carb) was measured by using Electrophorus electricus membrane vesicles, a simple filtration assay and flame emission spectroscopy. The dependence of the ratios of rate coefficients on the concentration of ligand and inhibitors was examined in detail. The inhibition constants of d-tubocurarine and caffeine were estimated to be about 31 nM and 0.84 mM, respectively, on the basis of a simple competitive inhibition scheme, and that of procaine was estimated to be 0.11 mM on the basis of a simple noncompetitive one.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002110:Caffeine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004593:Electrophorus; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D008433:Mathematics; D008954:Models, Biological; D011343:Procaine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007473:Ion Channels; D011950:Receptors, Cholinergic; D002110:Caffeine; D011343:Procaine; D002217:Carbachol; D008094:Lithium