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Vol. 60, Issue 3, 568-576, September 2001
3
4 Nicotinic Acetylcholine
Receptors Stably Expressed in Human Embryonic Kidney 293 Cells
Department of Pharmacology, Georgetown University School of
Medicine, Washington, DC
Effects of agonists on rat 
3
4 nicotinic acetylcholine receptors
expressed in KX34R2 cells [human embryonic kidney
293-derived cells] were studied. The potencies of seven agonists
varied over a 7000-fold range, with a rank order of epibatidine 
A85380 > cytisine 
1,1-dimethyl-4-phenyl-piperazinium
iodide (DMPP) nicotine > acetylcholine > carbachol. The efficacies of all of the agonists studied here were
similar except for DMPP, which seemed to be a partial agonist compared
with nicotine and acetylcholine. Nicotine and carbachol desensitized
the receptors in a time- and concentration-dependent manner. The
EC50 values for nicotine and carbachol to desensitize the
receptors during a 60-min exposure were 3 and 51 µM, respectively,
indicating that these agonists are more potent at desensitizing the
receptors than at activating them. The function of the receptors
recovered from agonist-induced desensitization rapidly and almost
completely. The half-time for recovery of function from desensitization
after a 60-min treatment with nicotine increased with the concentration
of nicotine used to desensitize the receptors. In contrast, no such
concentration dependence for time to recovery of function was found
when carbachol was used to desensitize the receptors. We propose that
this difference may be due to the cell permeability of nicotine,
allowing it to enter and be sequestered inside of cells and then slowly
diffuse out to maintain receptor desensitization. After a 5-day
exposure to 100 µM nicotine, the receptors were completely
desensitized, but receptor function recovered to 83% of control values
with a half-time of about 10.5 min. Although the number of nicotinic receptor binding sites measured with
(±)-[3H]epibatidine was increased during the
chronic treatment with nicotine, no increase in function was detected.
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