Effect of forskolin on acetylcholine-induced current in rat pheochromocytoma cells.
OBJECTIVE
To study the effect of forskolin on the nicotinic receptor (NicR) of PC12 cells.


METHODS
The acetylcholine (ACh)-induced current (IACh) was measured on PC12 cells by whole-cell clamp technique.


RESULTS
The IACh could be blocked by d-tubocurarine chloride and atropine had no effect on IACh. Infusion of forskolin (1-50 mumol.L-1) caused an inhibition on IACh, which was reversible, concentration-dependent, and voltage-independent. Preincubation with 8-bromo-adenosine-3', 5'-adenosine monophosphate (8-Br-cAMP), a cell-permeable cAMP analog which preferentially activated cyclic AMP-dependent protein kinase (CADPK), for 20 min, did not affect the IACh and the inhibitory effect of forskolin. Infusion of 1,9-dideoxyforskolin, an analog of forskolin which did not activate adenyl cyclase, also caused an inhibition on IACh.


CONCLUSIONS
The inhibitory effect of forskolin on IACh in PC12 cells is not mediated by activating the adenyl cyclase. Probably, the lipophilic forskolin acts via perturbing the plasma membrane lipid structure and altering the function of the NicR.
Shi
L J
LJ
Department of Physiology, Beijing Medical College of PLA, Beijing 100071, China. shilijun@btamail.net.cn
Liu
L A
LA
Wang
C A
CA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010673:Pheochromocytoma / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects*
D011978:Receptors, Nicotinic; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D000109:Acetylcholine; C047983:1,9-dideoxyforskolin