title: Inhibitory effects of ginsenoside-rb2 on nicotinic stimulation-evoked catecholamine secretion.
abstract: The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 (3~30 µM), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 (10 µM) also time-dependently inhibited the CA secretion evoked by DMPP (100 µM, a selective neuronal nicotinic receptor agonist) and high K(+) (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 (50 µg/mL), the secretory responses of CA evoked by veratridine (a selective Na(+) channel activator (50 µM), Bay-K-8644 (an L-type dihydropyridine Ca(2+) channel activator, 10 µM), and cyclopiazonic acid (a cytoplasmic Ca(2+)-ATPase inhibitor, 10 µM) were significantly reduced, respectively. Interestingly, in the simultaneous presence of Rb2 (10 µM) and L-NAME (an inhibitor of NO synthase, 30 µM), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 (10 µM) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 is mediated by inhibiting both the influx of Ca(2+) and Na(+) into the adrenomedullary chromaffin cells and also by suppressing the release of Ca(2+) from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade.
authors.affiliation: Department of Internal Medicine (Division of Pulmonary and Critical Care Medicine), Veterans Health Service Medical Center, Seoul 134-791, Korea.
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lim
authors.affiliation: Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Medicine, Chosun University, Gwangju 501-759, Korea.
authors.forename: Dong-Yoon
authors.initials: DY
authors.lastname: Lim
keywords: Adrenal Medulla; Catecholamine secretion; Ginsenoside-Rb2 (Rb2); NO production; Nitric oxide synthase (NOS)