Neostigmine competitively inhibited nicotinic acetylcholine receptors in sympathetic neurons.
The present experiment investigates the effect of neostigmine on nicotinic acetylcholine receptors (nAChRs) in the cultured neurons from neonatal rat superior cervical ganglia (SCG). Using whole-cell patch clamp techniques, we found that the amplitudes of the currents induced by 50 microM dimethylphenylpiperazinium (DMPP) were 21.5+/-10.7%, 52.9+/-9.2% and 86.9+/-4.9% depressed at the increased concentrations of neostigmine 100, 200 and 400 microM, respectively. The inhibition of neostigmine decreased gradually with the increased concentration of nicotine from 10 to 160 microM. Lineweaver-Burk's double-reversible plot illustrated that neostigmine blocked neuronal nAChRs in a competitive manner. Hyperpolarization of membrane potential from -40 mV to -100 mV did not significantly influence the blockade of neostigmine. Neostigmine could not accelerate the decay of the DMPP-induced currents, neither evoke any detectable currents in SCG neurons. The results indicate that neostigmine depress neuronal nAChRs in a competitive, concentration-dependent and voltage-independent manner, and can not facilitate desensitization of the receptors. The present data suggest that neostigmine blocks neuronal nAChRs by interacting with the ACh binding sites of the receptors.
Zheng
J Q
JQ
Institute of Pharmacology & Toxicology, Academy of Military Medical Sciences, Beijing, China.
He
X P
XP
Yang
A Z
AZ
Liu
C G
CG
D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009388:Neostigmine / Q000378:metabolism / Q000494:pharmacology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000648:ultrastructure*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000187:drug effects* / Q000648:ultrastructure*
D002800:Cholinesterase Inhibitors; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D009388:Neostigmine; D004246:Dimethylphenylpiperazinium Iodide