Cyclic AMP inhibits both nicotine-induced actin disassembly and catecholamine secretion from bovine adrenal chromaffin cells.

As part of our studies on the functional role of the cytoskeleton in exocytosis we have reported (Cheek, T.R., and Burgoyne, R.D. (1986) FEBS Lett. 207, 110-114) that a calcium-independent transient disassembly of cortical actin filaments occurs on activation of the chromaffin cell nicotinic receptor but not when the cell is exposed to 55 mM K+. In order to determine whether this actin disassembly is required, in conjunction with a rise in intracellular Ca2+, to elicit a maximum secretory response from these cells, we have examined the relationship between actin disassembly, the elevation in intracellular Ca2+, and secretion in detail. The results show that the dose dependence of nicotine-induced secretion and actin disassembly are essentially identical with maximal effects at a dose of nicotine that produced a submaximal rise in intracellular Ca2+. Intracellular cAMP, elevated by three independent means, did not inhibit 55 mM K+-induced secretion but inhibited nicotine-induced secretion. Forskolin inhibited actin disassembly while not affecting the rise in intracellular Ca2+. These results demonstrate that a close inter-relationship exists between the secretory response and actin disassembly and provide further evidence suggesting that actin disassembly could be required in addition to the rise in intracellular Ca2+ in order to elicit a maximal secretory response in chromaffin cells. In addition, the results point to a role for cAMP in the regulation of stimulus-induced actin disassembly.