Enhancement of depolarization-dependent neurosecretion from PC12 cells by forskolin-induced elevation of cyclic AMP

C. S. Rabe, J. Schneider, R. McGee

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33 Scopus citations

Abstract

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 μM 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 μM forskolin. Release of NE elicited by depolarization with carbachol and veratridine also was enhanced by 1 μM 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.

Original languageEnglish (US)
Pages (from-to)371-384
Number of pages14
JournalJournal of Cyclic Nucleotide Research
Volume8
Issue number6
StatePublished - 1982

ASJC Scopus subject areas

  • Medicine(all)

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