RT Journal Article SR Electronic T1 Correlation of activation of Ca2+/calmodulin-dependent protein kinase II with catecholamine secretion and tyrosine hydroxylase activation in cultured bovine adrenal medullary cells. JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1041 OP 1047 VO 46 IS 6 A1 M Tsutsui A1 N Yanagihara A1 E Miyamoto A1 A Kuroiwa A1 F Izumi YR 1994 UL http://molpharm.aspetjournals.org/content/46/6/1041.abstract AB We have investigated the activation of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in cultured bovine adrenal medullary cells. The activation was assayed as an increase in the Ca(2+)-independent (autonomous) activity of CaM kinase II, using the synthetic substrate Syntide-2. Incubation of cells with acetylcholine increased the Ca(2+)-independent activity in a time (20 sec to 5.0 min)- and concentration (10-300 microM)-dependent manner. These curves were closely correlated with those of catecholamine secretion and tyrosine hydroxylase activation. Removal of extracellular Ca2+ completely abolished the stimulatory effects of acetylcholine on the Ca(2+)-independent activity, as well as on catecholamine secretion and activation of tyrosine hydroxylase. Nicotine but not muscarine increased the Ca(2+)-independent activity as potently as did acetylcholine, and hexamethonium but not atropine completely blocked the acetylcholine-induced increase. In 32P-labeled cells, acetylcholine stimulated the phosphorylation of a 50-kDa protein that was immunoprecipitated with an anti-brain CaM kinase II antibody. These results suggest that acetylcholine stimulates CaM kinase II activity through nicotinic acetylcholine receptor-mediated influx of Ca2+ and that the activation of CaM kinase II is closely related to catecholamine secretion and tyrosine hydroxylase activation in cultured adrenal medullary cells.