NEOSTIGMINE COMPETITIVELY INHIBITED NICOTINIC ACETYLCHOLINE-RECEPTORSIN SYMPATHETIC NEURONS

The present experiment investigates the effect of neostigmine on nicot inic acetylcholine receptors (nAChRs) in the cultured neurons from neo natal rat superior cervical ganglia (SCG). Using whole-cell patch clam p techniques, we found that the amplitudes of the currents induced by 50 mu M dimethylphenylpiperazinium (DMPP) were 21.5+/-10.7%, 52.9+/-9. 2% and 86.9+/-4.9% depressed at the increased concentrations of neosti gmine 100, 200 and 400 mu M, respectively. The inhibition of neostigmi ne decreased gradually with the increased concentration of nicotine fr om 10 to 160 mu M. Lineweaver-Burk's double-reversible plot illustrate d that neostigmine blocked neuronal nAChRs in a competitive manner. Hy perpolarization of membrane potential from -40 mV to -100 mV did not s ignificantly influence the blockade of neostigmine. Neostigmine could not accelerate the decay of the DMPP-induced currents, neither evoke a ny detectable currents in SCG neurons. The results indicate that neost igmine depress neuronal nAChRs in a competitive, concentration-depende nt and voltage-independent manner, and can not facilitate desensitizat ion of the receptors. The present data suggest that neostigmine blocks neuronal nAChRs by interacting with the ACh binding sites of the rece ptors.