Acute elevation of cyclic AMP does not alter the ion-conducting properties of the neuronal nicotinic acetylcholine receptor of PC12 cells.
The nicotinic acetylcholine receptor of Torpedo californica has been shown to be subject to cyclic AMP-dependent phosphorylation, raising the possibility that nicotinic receptors may be regulatable by phosphorylation. To investigate this possibility for a neuronal nicotinic receptor, we have studied the effects of elevation of cyclic AMP on the ion-conducting properties of the nicotinic receptor of PC12 cells. The cyclic AMP content of the cells was altered by exposure to various concentrations of forskolin (an activator of adenylate cyclase) for periods of time ranging from 1 to 40 min. Receptor activation then was measured as agonist-induced influx of 86Rb+ into the cells. Throughout a variety of conditions, no changes in agonist-induced ion influx were detected. This was true regardless of the concentration of agonist used, the duration of receptor stimulation that was measured, the concentration of forskolin employed, or the duration of elevation of cyclic AMP prior to receptor activation. Experiments designed to measure receptor desensitization also were unable to detect any differences upon elevation of cyclic AMP. Finally, the antagonism of receptor activation by substance P also was not affected by elevation of cyclic AMP. Thus, no evidence could be obtained in these cells supporting the hypothesis that a neuronal nicotinic acetylcholine receptor can be acutely regulated by changes in cellular cyclic AMP.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism*; D004224:Diterpenes / Q000494:pharmacology; D007473:Ion Channels / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism
D004224:Diterpenes; D007473:Ion Channels; D011978:Receptors, Nicotinic; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D012413:Rubidium