Biomolecules & Therapeutics 2008; 16(2): 147-160  
Inhibitory Mechanism of Polyphenol Compounds Isolated from Red Wine on Catecholamine Release in the Perfused Rat Adrenal Medulla
Byung-Sik YU1, Woo-Seok KO1, and Dong-Yoon LIM2*
1Department of Anesthesiology, College of Medicine, Chosun University, Gwangju 501-759, KOREA
2Department of Pharmacology, College of Medicine, Chosun University, Gwangju 501-759, KOREA
Received: June 5, 2008; Accepted: June 25, 2008; Published online: June 1, 2008.
© The Korean Society of Applied Pharmacology. All rights reserved.

Abstract
The present study was designed to examine effects of polyphenolic compounds isolated from red wine (PCRW) on the release of catecholamines (CA) from the isolated perfused model of the rat adrenal medulla, and to clarify its mechanism of action. PCRW (20~180 μg/mL), given into an adrenal vein for 90 min, caused inhibition of the CA secretory responses evoked by ACh (5.32 mM), high K+ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic NN receptor agonist, 100 μM) and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 μM) in dose- and time-dependent fashion. PCRW itself did not affect basal CA secretion (data not shown). Following the perfusion of PCRW (60 μg/mL), the secretory responses of CA evoked by Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 μM), cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 μM) and veratridine (an activator of voltage-dependent Na+ channels, 10 μM) were also markedly blocked, respectively. Interestingly, in the simultaneous presence of PCRW (60 μg/mL) and L-NAME (a selective inhibitor of NO synthase, 30 μM), the inhibitory responses of PCRW on the CA secretion evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid were recovered to considerable level of the corresponding control release compared with those effects of PCRW-treatment alone. Practically, the amount of NO released from adrenal medulla after loading of PCRW (180 μg/mL) was significantly increased in comparison to the corresponding basal released level. Collectively, these results obtained here demonstrate that PCRW inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal gland of the normotensive rats. It seems that this inhibitory effect of PCRW is mediated by blocking the influx of both ions through Na+ and Ca2+ channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the release of Ca2+ from the cytoplasmic calcium store, which are due at least partly to the increased NO production through the activation of nitric oxide synthase. Based on these data, it is also thought that PCRW may be beneficial to prevent or alleviate the cardiovascular diseases, such as hypertension and angina pectoris.
Keywords: PCRW, Catecholamine Release, Adrenal Medulla, Nitric Oxide Synthase (NOS), NO release

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