ANTICHOLINESTERASE INDUCES NICOTINIC RECEPTOR MODULATION

The effects of carbamate anticholinesterases, pyridostigmine and physo stigmine, on the function of the nicotinic receptor (nAChR) in TE671 c ells was studied, precluding their inhibition of acetylcholine hydroly sis by carbachol usage, In radioassay, the simultaneous application of carbachol and carbamates dose-dependently decreased carbachol-induced Na-22(+) influx, compared with carbachol activation alone. Increasing cell preincubation in the presence of carbamates, however, potentiate d influx at low concentrations in a time-dependent manner. This facili tating effect of carbamates, even at high concentrations, was signific antly increased by washing out these drugs and was blocked by pretreat ment with diisopropylfluorophosphate. Similar results were also obtain ed in whole-cell patch-clamp study. There were insignificant changes i n desensitization properties during facilitation. It is thus supposed that facilitation cannot be explained by the inhibition of acetylcholi ne hydrolysis, These results support a previous hypothesis that acetyl cholinesterase might modulate nAChR by an unknown mechanism. In additi on, the clinical effects of carbamates may be partly attributed to thi s facilitation, (C) 1998 John Wiley & Sons, Inc.