Modulation of neuronal nicotinic acetylcholine receptors by glucocorticoids.
OBJECTIVE
To investigate the nongenomic effect of the glucocorticoid corticosterone on nicotinic acetylcholine receptor (nAChR) in PC12 cells.


METHODS
The acetylcholine (ACh)-induced current was measured on nerve growth factor differentiated PC12 cells using whole-cell patch-clamp techniques.


RESULTS
The ACh-induced current (IACh) proved to be generated through neuronal nAChR. When ACh (30 micromol/L) was applied simultaneously with corticosterone (0.1 - 10 micromol/L), the decay of IACh was faster with slight inhibition on the peak current amplitude. Pretreating PC12 cells with corticosterone augmented the inhibition on the peak IACh and did not alter receptor desensitization. Bovine serum albumin-conjugated corticosterone (0.1 - 10 micromol/L) had the inhibition similar to corticosterone. The rapid effect induced by corticosterone was reversible, concentration-dependent, and voltage-independent.


CONCLUSIONS
Corticosterone has rapid inhibitory effect on IACh, which is mediated by a nongenomic mechanism. It indicates that corticosterone binds to the specific site on the outer cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the IACh in a noncompetitive manner, thus controlling the immediate catecholamine release from the sympathetic cells.
Shi
Li-Jun
LJ
Department of Physiology, Beijing Medical College of PLA, Beijing 100071, China. l.j.shi@263.net
Liu
Ling-Ai
LA
Cheng
Xiao-Hong
XH
Wang
Chun-An
CA
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011978:Receptors, Nicotinic; D000109:Acetylcholine; D003345:Corticosterone