Acetylcholine receptor-controlled ion translocation caused by phenyltrimethylammonium and nereistoxin: simple estimation of equilibrium constants of the minimal model.
The rate of slow Li+ influx and the fraction of active form of acetylcholine receptor (AChR) of Electrophorus electricus membrane vesicles at equilibrium between the active and desensitized forms of the receptor were measured in the presence of various concentrations of phenyltrimethylammonium (PTA) and nereistoxin (NTX), by a simple filtration assay and flame emission spectroscopy. The equilibrium constants of these ligands in the minimal model, which accounts for the AChR-mediated ion flux, were estimated simply from these two measurements, since the equilibrium constants for acetylcholine (ACh) and carbamylcholine (Carb) estimated from two kinetic measurements agreed well with those estimated from five sophisticated kinetic measurements of AChR-mediated ion fluxes. PTA showed high potency but not high efficacy, and showed inhibition when large doses were applied. NTX showed both low potency and low efficacy and acted as an inhibitor when it was added with Carb. The apparent dissociation constants of these three agonists evaluated from the minimal model and the equilibrium constants agreed with those obtained by assay of inhibition of radiolabeled ligand binding.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D004593:Electrophorus; D007477:Ions / Q000378:metabolism*; D007700:Kinetics; D008094:Lithium / Q000378:metabolism; D008387:Marine Toxins / Q000494:pharmacology*; D008954:Models, Biological; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000378:metabolism* / Q000502:physiology
D007477:Ions; D008387:Marine Toxins; D000644:Quaternary Ammonium Compounds; D011950:Receptors, Cholinergic; C025633:nereistoxin; C009571:phenyltrimethylammonium; D002217:Carbachol; D008094:Lithium