Characterization of ginseng saponin ginsenoside-Rg(3) inhibition of catecholamine secretion in bovine adrenal chromaffin cells

Since ginsenoside-Rg(3), one of the panaxadiol saponins isolated from the g inseng root, significantly inhibited the secretion of catecholamines from b ovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the prope rties of ginsenoside-Rg(3) inhibition were investigated. Although ginsenosi de-Rg(3) inhibited the secretion evoked by ACh in a concentration-dependent manner, it affected the secretion stimulated by high K+ or veratridine, an activator of the voltage-sensitive Ca2+ or Na+ channels, only slightly. Th e ACh-induced Na+ and Ca2+ influxes into the cells were also reduced by gin senoside-Rg(3). The inhibitory effect of this saponin on the secretion of c atecholamines was not altered by increasing the external concentration of A Ch or Ca2+. The ACh-evoked secretion of catecholamines was completely resto red in cells that were preincubated with 10 muM ginsenoside-Rg(3) and then incubated without the saponin, whereas secretion was not completely restore d in cells that were preincubated with 30 muM of this compound. Above 30 mu M ginsenoside-Rg(3) increased the fluorescence anisotropy of diphenylhexatr iene in the cells. Furthermore, the inhibitory effect of ginsenoside-Rg(3) at 30 AM on the ACh-evoked secretion of catecholamines was dependent upon t he preincubation time, but this was not the case at 10 muM. These results s trongly suggest that ginsenoside-Rg(3), blocks the nicotinic ACh receptor-o perated cation channels, inhibits Na+ influx through the channels, and cons equently reduces both Ca2+ influx and catecholamine secretion in bovine adr enal chromaffin cells. In addition to this action, the ginsenoside at highe r concentrations modulates the fluidity of the plasma membrane, which proba bly contributes to the observed reduction in the secretion of catecholamine s. (C) 2001 Elsevier Science Inc. All rights reserved.