title: Cyclic AMP inhibits both nicotine-induced actin disassembly and catecholamine secretion from bovine adrenal chromaffin cells.
abstract: 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.
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000313:Adrenal Medulla / Q000648:ultrastructure; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009538:Nicotine / Q000494:pharmacology*
chemical_list: D000199:Actins; D002395:Catecholamines; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009538:Nicotine; D002772:Cholera Toxin; D000242:Cyclic AMP