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 preparations of adrenal chromaffin cells and was compared with other known stimulants in this system. 2. (+)Anatoxin-a was found to be a potent stimulant of catecholamine secretion with EC50=545.7 nM, which was 5.8 times as strong as nicotine (EC50=3,165 nM). (+)Anatoxin-a action was time dependent and saturable. 3. The pharmacological characteristics of (+)anatoxin-a were tested by using nicotinic and muscarinic antagonists (mecamylamine and atropine, respectively). Mecamylamine (1 microM) and atropine (100 microM) inhibited the secretion induced by (+)anatoxin-a (1 microM), as well as that induced by nicotine (10 microM), acetylcholine (10 microM and 100 microM) and oxotremorine-M (100 microM). 4. The calcium requirement for (+)anatoxin-a action was tested in comparison with the aforementioned stimulants. Addition of the calcium antagonist verapamil (10 microM) or the calcium chelator EGTA (3 mM) reduced all stimulants' action. 5. These results show that the (+)enantiomer of anatoxin-a is both dose and time dependent. Its action is mediated through the classical operation of the nicotinic acetylcholine receptor, by using calcium influx.
Dar
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Department of Clinical Biochemistry, Rambam Medical Center, Haifa, Israel. ddar@irp.nida.nih.gov
Zinder
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D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D019439:Chromaffin Cells / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008387:Marine Toxins / Q000737:chemistry / Q000494:pharmacology*; D052998:Microcystins; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009498:Neurotoxins / Q000737:chemistry / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D013237:Stereoisomerism; D013997:Time Factors; D014326:Tropanes; D014700:Verapamil / Q000494:pharmacology
D001427:Bacterial Toxins; D002121:Calcium Channel Blockers; D002395:Catecholamines; D002614:Chelating Agents; D000087522:Cyanobacteria Toxins; D008387:Marine Toxins; D052998:Microcystins; D018727:Muscarinic Antagonists; D009498:Neurotoxins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D014326:Tropanes; D004533:Egtazic Acid; C509783:anatoxin a; D014700:Verapamil; D002118:Calcium