Influence of lobeline on catecholamine release from the isolated perfused rat adrenal gland

• Published in: Autonomic neuroscience 2004-01, Vol.110 (1), p.27-35
• Main Authors: Lim, Dong-Yoon, Kim, Yang-Soo, Miwa, Soichi
• Format: Article
• Language: English
• Subjects: (4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride - pharmacology; 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester - pharmacology; Acetylcholine - metabolism; Acetylcholine - pharmacology; Adrenal gland; Adrenal Medulla - drug effects; Adrenal Medulla - secretion; Animals; Biological and medical sciences; Calcium Channels, L-Type - drug effects; Calcium Channels, L-Type - metabolism; Catecholamine secretion; Catecholamines - secretion; Chromaffin Cells - drug effects; Chromaffin Cells - secretion; Dimethylphenylpiperazinium Iodide - pharmacology; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Lobeline (from Lobelia inflata); Lobeline - pharmacology; Male; Muscarinic Agonists - pharmacology; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Nicotinic antagonist; Perfusion; Peripheral nervous system. Autonomic nervous system. Neuromuscular transmission. Ganglionic transmission. Electric organ; Potassium - metabolism; Potassium - pharmacology; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Reaction Time - physiology; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 1566-0702; 1872-7484
• DOI: 10.1016/j.autneu.2003.10.001

It has been shown that lobeline (α-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 μM) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32×10 −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 + (5.6×10 −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 μM), 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 μM), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh (5.32×10 −3 M) and high K + (5.6×10 −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.