Influence of lobeline on catecholamine release from the isolated perfused rat adrenal gland.
It has been shown that lobeline (alpha-lobeline) is a lipophilic, nonpyridine, naturally occurring alkaloid obtained from Indian tobacco, Lobelia inflata. The present study was attempted to investigate the effect of lobeline on secretion of catecholamines (CA) evoked by ACh, high K(+), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP) and (3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyl trimethyl ammonium chloride (McN-A-343) from the isolated perfused rat adrenal gland and to establish the mechanism of its action. l-Lobeline (30-300 microM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 x 10(-3) M), DMPP (10(-4) M for 2 min) and McN-A-343 (10(-4) M for 2 min). However, lower dose of lobeline did not affect CA secretion by high K(+) (5.6 x 10(-2) M), higher dose of it reduced greatly CA secretion of high K(+). l-Lobeline itself did also fail to affect basal catecholamine output. Furthermore, in adrenal glands loaded with lobeline (100 microM), CA secretory response evoked by methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)-pyridine-5-carboxylate (Bay-K-8644), an activator of L-type Ca(2+) channels was markedly inhibited while CA secretion by cyclopiazonic acid, an inhibitor of cytoplasmic Ca(2+)-ATPase was not affected. However, nicotine (30 microM), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh (5.32 x 10(-3) M) and high K(+) (5.6 x 10(-2) M) followed by great inhibition later, while responses evoked by DMPP (10(-4) M for 2 min) and McN-A-343 (10(-4) M for 2 min) were greatly inhibited. Taken together, these results suggest that lobeline inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors. Lobeline at lower dose does not affect that by membrane depolarization, but at larger dose inhibits that. It is thought that this inhibitory effect of lobeline may be mediated by blocking the calcium influx into the rat adrenal medullary chromaffin cells without the inhibition of Ca(2+) release from the cytoplasmic calcium store, which is relevant to its nicotinic antagonistic activity. It also seems that there is a difference in the mode of action between nicotine and lobeline in rat adrenomedullary CA secretion.
Lim
Dong-Yoon
DY
Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, South Korea. dylim@chosun.ac.kr
Kim
Yang-Soo
YS
Miwa
Soichi
S
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008120:Lobeline / Q000494:pharmacology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010477:Perfusion; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism
D020746:Calcium Channels, L-Type; D002395:Catecholamines; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D009538:Nicotine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008120:Lobeline; D000109:Acetylcholine; D011188:Potassium