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KMID : 0811720090130030229
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Korean Journal of Physiology & Pharmacology
2009 Volume.13 No. 3 p.229 ~ p.239
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Provinol Inhibits Catecholamine Secretion from the Rat Adrenal Medulla
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Lee Jung-Hee
Seo Yu-Seung
Lim Dong-Yoon
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Abstract
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The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3∼3 μg/ml) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited 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). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 μg/ml), the secretory
responses of CA evoked by Bay-K-8644 (a voltage-dependent 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 significantly reduced. Interestingly, in the simultaneous presence of provinol (1 μg/ml) plus L-NAME (a selective inhibitor of NO synthase, 30 μM), the CA secretory responses evoked by ACh, high K＋ , DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 μg/ml) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of Ca2＋ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.
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KEYWORD
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Provinol, Catecholamine secretion, Adrenal medulla, Cholinergic receptors, Nitric oxide
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