A possible involvement of cyclic AMP in the expression of desensitization of the nicotinic acetylcholine receptor. A study with forskolin and its analogs.
Forskolin, an activator of adenylate cyclase, and its analogs were studied on the nicotinic acetylcholine receptor-ion channel complex (AChR) of rat and frog skeletal muscles. At nanomolar concentrations, forskolin caused desensitization of the AChR located at the junctional region of innervated and the extrajunctional region of chronically denervated rat soleus muscles. The desensitization of the AChR occurred without alteration of the conducting state (channel lifetime, conductance or bursting) as shown by single channel currents. Accordingly, forskolin decreased the peak amplitude of the repetitive evoked endplate currents in frog sartorius muscles. These findings taken together with the good correlation found between the effects of forskolin and its analogs on the desensitization of the nicotinic AChR and their ability to activate adenylate cyclase suggested a possible involvement of phosphorylation of AChR via cyclic AMP on the desensitization process.
E X
EX
Albuquerque
S S
SS
Deshpande
Y
Y
Aracava
M
M
Alkondon
J W
JW
Daly
D000110:Acetylcholinesterase / Q000032:analysis; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000031:analogs & derivatives / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology*; D004789:Enzyme Activation; D005260:Female; D007473:Ion Channels / Q000187:drug effects; D009132:Muscles / Q000201:enzymology; D011494:Protein Kinases / Q000378:metabolism; D011898:Ranidae; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects*
D007473:Ion Channels; D011978:Receptors, Nicotinic; D005576:Colforsin; D000242:Cyclic AMP; D011494:Protein Kinases; D000110:Acetylcholinesterase; D000262:Adenylyl Cyclases