CATECHOLAMINE SECRETION FROM BOVINE ADRENAL CHROMAFFIN CELLS INDUCED BY THE DEXTROROTATORY ISOMER OF ANATOXIN-A

1. The nicotinic agonist (+)anatoxin-a was studied in acute preparatio ns of adrenal chromaffin cells and was compared with other known stimu lants in this system. 2. (+)Anatoxin-a was found to be a potent stimul ant of catecholamine secretion with EC50 = 545.7 nM, which was 5.8 tim es as strong as nicotine (EC50 = 3,165 nM). (+)-Anatoxin-a action was time dependent and saturable. 3. The pharmacological characteristics o f (+)anatoxin a were tested by using nicotinic and muscarinic antagoni sts (mecamylamine and atropine, respectively). Mecamylamine (1 mu M) a nd atropine (100 mu M) inhibited the secretion induced by (+)anatoxin- a (1 mu M), as well as that induced by nicotine (10 mu M), acetylcholi ne (10 mu M and 100 mu M) and oxotremorine-M (100 mu M) 4. The calcium requirement for (+)anatoxin a action was tested in comparison with th e aforementioned stimulants, Addition of the calcium antagonist verapa mil (10 mu M) or the calcium chelator EGTA (3 mM) reduced all stimulan ts' action. 5. These results show that the (+)enantiomer of anatoxin-a is both dose and time dependent. Its action is mediated through the c lassical operation of the nicotinic acetylcholine receptor, by using c alcium influx. (C) 1998 Elsevier Science Inc.