Influence of polyphenolic compounds isolated from Rubus coreanum on catecholamine release in the rat adrenal medulla.
The aim of the present study was to investigate whether polyphenolic compounds isolated from wine brewed from Rubus coreanum MIQUEL (PCRC) may affect the release of catecholamine (CA) from the isolated perfused rat adrenal medulla, and to establish its mechanism of action. PCRC (20-180 microg/mL) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM), high K+ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic Nn receptor agonist, 100 microM) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 microM). Also, in the presence of PCRC (60 microg/mL), the secretory responses of CA evoked by Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 microM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 microM) were significantly reduced, respectively. In the simultaneous presence of PCRC (60 microg/mL) and L-NAME (an inhibitor of NO synthase, 30 microM), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high K+, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of PCRC alone. Taken together, these results obtained from the present study demonstrate that PCRC inhibits the CA secretory responses from the isolated perfused adrenal gland of the normotensive rats evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is exerted by inhibiting both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of Ca2+ into the cytoplasmic calcium store partly through the increased NO production due to the activation of nitric oxide synthase (NOS), which are at least relevant to the direct interaction with the nicotinic receptor itself. It is also thought that PCRC might be effective in prevention of cardiovascular disease.
Kee
Young-Woo
YW
Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, Korea.
Lim
Dong-Yoon
DY
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 / Q000494:pharmacology; D000313:Adrenal Medulla / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism*; D018679:Cholinergic Agonists / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010477:Perfusion; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027824:Rosaceae / Q000737:chemistry*; D013997:Time Factors; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D002395:Catecholamines; D018679:Cholinergic Agonists; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D014665:Vasodilator Agents; D009569:Nitric Oxide; D004246:Dimethylphenylpiperazinium Iodide; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D019001:Nitric Oxide Synthase; D000252:Calcium-Transporting ATPases; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; C000543:cyclopiazonic acid