title: Inhibitory Effects of Total Ginseng Saponin on Catecholamine Secretion from the Perfused Adrenal Medulla of SHRs.
abstract: There seems to be some controversy about the effect of total ginseng saponin (TGS) on the secretion of catecholamines (CA) from the adrenal gland. Therefore, the present study aimed to determine whether TGS can affect the CA release in the perfused model of the adrenal medulla isolated from spontaneously hypertensive rats (SHRs). TGS (15-150 μg/mL), perfused into an adrenal vein for 90 min, inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM) and high K(+) (56 mM, a direct membrane depolarizer) in a dose- and time-dependent fashion. TGS (50 μg/mL) also time-dependently inhibited the CA secretion evoked by 1.1-dimethyl-4 -phenyl piperazinium iodide (DMPP; 100 μM, a selective neuronal nicotinic receptor agonist) and McN-A-343 (100 μM, a selective muscarinic M1 receptor agonist). TGS itself did not affect basal CA secretion (data not shown). Also, in the presence of TGS (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 TGS (50 μg/mL) and Nω-nitro-L-arginine methyl ester hydrochloride [an inhibitor of nitric oxide (NO) synthase, 30 μM], the inhibitory responses of TGS on the CA secretion evoked by ACh, high K(+), DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid, and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of TGS-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of TGS (150 μg/mL) was greatly elevated compared to the corresponding basal released level. Taken together, these results demonstrate that TGS 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 medulla of the SHRs. It seems that this inhibitory effect of TGS 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, without the enhancement effect on the CA release. Based on these effects, it is also thought that there are some species differences in the adrenomedullary CA secretion between the rabbit and SHR.
authors.affiliation: Department of Neurosurgery, Chosun University School of Medicine, Gwangju 501-759, Korea.
authors.forename: Seok-Jeong
authors.initials: SJ
authors.lastname: Jang
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lim
authors.forename: Dong-Yoon
authors.initials: DY
authors.lastname: Lim
keywords: Adrenal medulla; Catecholamine secretion; Nitric oxide production; Nitric oxide synthase; total ginseng saponin