ISSN:
1432-1912
Keywords:
Forskolin
;
Phencyclidine
;
cAMP
;
Nicotinic acetylcholine receptor complex
;
Membrane properties
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Forskolin, a commonly used adenylate cyclase activator, was found to inhibit reversibly the carbachol-induced ion-translocating capacity of the nicotinic acetylcholine receptor (nAChR) on chick myotubes in a dose- (IC50 = 20 μM) and time-dependent manner. This effect was not correlated to increases in cellular cAMP. Forskolin, at a concentration (50 μM) that totally blocked the carbachol-induced 86Rb influx, caused no change in carbachol or α-bungarotoxin binding to chick myotube nAChR in situ. In contrast, in the presence of carbachol, forskolin inhibited (IC50 = 10 μM) the binding of 3H-phencyclidine, a putative nAChR ion-channel ligand, to Torpedo microsac nAChR. Inhibition of 3H-phencyclidine binding in the absence of carbachol was not complete. Membrane leakage studies on myotubes, measuring 3H-efflux from 2-deoxy-d(1-3H)-glucose loaded cells and electrophysiological measurements of membrane properties supported the interpretation that forskolin induced decreases in plasma membrane permeability. In conclusion, forskolin blocks the carbachol-mediated increase in permeability of the nAChR channel by (1) binding to the ion-channel (open state) and (2) generally perturbing the plasma membrane function possibly by interfering with the protein-lipid interface.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00164869
