Action of organophosphate anticholinesterases on the three conformational states of nicotinic receptor.
Organophosphate and other ligands were examined for binding on the membrane-bond nicotinic receptor at three conformational states. Soman (pinacolyl methylphosphonofluoridate), sarin (isopropyl methylphosphonofluoridate, tabun (ethyl N-dimethylphosphoramidocyanidate) and phencyclidine did not show any effect on the binding of [25I]alpha-cobrotoxin to the nicotinic receptor. However, VX, O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate, at concentrations higher than 10 umol/L exhibited profound inhibition on the equilibrium binding rates in a concentration-dependent manner. Agonist nicotine and antagonist d-tubocurarine also showed significant inhibitions.
Chi
M
M
Institute of Pharmacology and Toxicology, Beijing, China.
Sun
M
M
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D003039:Cobra Neurotoxin Proteins / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012999:Soman / Q000494:pharmacology; D014101:Torpedo; D014403:Tubocurarine / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D003039:Cobra Neurotoxin Proteins; D009943:Organophosphorus Compounds; D011978:Receptors, Nicotinic; C025154:alpha-cobratoxin; D012999:Soman; D010622:Phencyclidine; D014403:Tubocurarine