title: Cotinine inhibits catecholamine release evoked by cholinergic stimulation from the rat adrenal medulla.
abstract: The aim of the present study was to clarify whether cotinine affects the release of catecholamines (CA) from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, in comparison with the response of nicotine. Cotinine (0.3-3 mM), when perfused into an adrenal vein for 60 min, inhibited CA secretory responses evoked by ACh (5.32 mM), DMPP (a selective neuronal nicotinic agonist, 100 microM for 2 min) and McN-A-343 (a selective muscarinic M1-agonist, 100 microM for 2 min) in dose- and time-dependent manners. However, cotinine did not affect CA secretion by high K+ (56 mM). Cotinine itself also failed to affect basal CA output. Furthermore, in the presence of cotinine (1 mM), CA secretory responses evoked by Bay-K-8644 (an activator of L-type Ca2+ channels, 10 microM) and cyclopiazonic acid (an inhibitor of cytoplasmic Ca2+-ATPase, 10 microM) were relative time-dependently attenuated. However, nicotine (30 microM), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh and high K+, followed by the inhibition later, while it time-dependently depressed the CA release evoked by McN-A-343 and DMPP. Taken together, these results suggest that cotinine inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by the direct membrane-depolarization. It seems that this inhibitory effect of cotinine may be exerted by the cholinergic blockade, which is associated with blocking both the calcium influx into the rat adrenal medullary chromaffin cells and Ca2+ release from the cytoplasmic calcium store. It also seems that there is a big difference in the mode of action between cotinine and nicotine in the rat adrenomedullary CA secretion.
authors.affiliation: Department of Internal Medicine (Cardiology), College of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Young-Yeop
authors.initials: YY
authors.lastname: Koh
authors.forename: Seok-Jeong
authors.initials: SJ
authors.lastname: Jang
authors.forename: Dong-Yoon
authors.initials: DY
authors.lastname: Lim
mesh_terms: D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000493:pharmacokinetics; D000109:Acetylcholine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000313:Adrenal Medulla / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D003367:Cotinine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004246:Dimethylphenylpiperazinium Iodide / Q000008:administration & dosage / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066298:In Vitro Techniques; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics; D011189:Potassium Chloride / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002395:Catecholamines; D007211:Indoles; D004246:Dimethylphenylpiperazinium Iodide; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D011189:Potassium Chloride; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003367:Cotinine; D000109:Acetylcholine; C000543:cyclopiazonic acid