Enhancement of depolarization-dependent neurosecretion from PC12 cells by forskolin-induced elevation of cyclic AMP.
The effects of elevated intracellular cyclic AMP on the release of neurotransmitters was studied using the clonal pheochromocytoma cell line, PC12, and forskolin, a direct activator of adenylate cyclase. Intracellular cyclic AMP concentrations ranging from 8 to 400 times basal levels were achieved with 0.1 to 100 uM forskolin. Unstimulated release of neurotransmitters was unchanged by any concentration of forskolin. However, K+-stimulated release of both norepinephrine (NE) and acetylcholine was enhanced by 0.1 to 10 uM forskolin. Release of NE elicited by depolarization with carbachol and veratridine also was enhanced by 1 uM forskolin. Enhancement of release was reversed by higher concentrations of forskolin, especially in the presence of a phosphodiesterase inhibitor (RO 20-1724) which caused very large increases in cyclic AMP content. The enhancement of transmitter release from the PC12 cells occurred without concomitant changes in agonist-stimulated ion flux through the acetylcholine receptor ion channel, or in depolarization-dependent uptake of 45Ca++. Thus, increasing the cyclic AMP content of PC12 cells fails to initiate neurosecretion but appears to facilitate some element in the secretion process subsequent to Ca++ influx.
D000310:Adrenal Gland Neoplasms / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D005576:Colforsin; D000242:Cyclic AMP / Q000378:metabolism* / Q000502:physiology; D004224:Diterpenes / Q000494:pharmacology*; D007477:Ions; D009374:Neoplasms, Experimental / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010673:Pheochromocytoma / Q000378:metabolism*; D051381:Rats
D004224:Diterpenes; D007477:Ions; D018377:Neurotransmitter Agents; D005576:Colforsin; D000242:Cyclic AMP