Characterization of ginseng saponin ginsenoside-Rg3 inhibition of catecholamine secretion in bovine adrenal chromaffin cells

Since ginsenoside-Rg(3), one of the panaxadiol saponins isolated from the ginseng root, significantly inhibited the secretion of catecholamines from bovine adrenal chromaffin cells stimulated by acetylcholine (ACh), the properties of ginsenoside-Rg(3) inhibition were investigated. Although ginsenoside-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. The ACh-induced Na+ and Ca2+ influxes into the cells were also reduced by ginsenoside-Rg(3). The inhibitory effect of this saponin on the secretion of catecholamines was not altered by increasing the external concentration of ACh or Ca2+. The ACh-evoked secretion of catecholamines was completely restored in cells that were preincubated with 10 muM ginsenoside-Rg(3) and then incubated without the saponin, whereas secretion was not completely restored in cells that were preincubated with 30 muM of this compound. Above 30 muM ginsenoside-Rg(3) increased the fluorescence anisotropy of diphenylhexatriene in the cells. Furthermore, the inhibitory effect of ginsenoside-Rg(3) at 30 AM on the ACh-evoked secretion of catecholamines was dependent upon the preincubation time, but this was not the case at 10 muM. These results strongly suggest that ginsenoside-Rg(3), blocks the nicotinic ACh receptor-operated cation channels, inhibits Na+ influx through the channels, and consequently reduces both Ca2+ influx and catecholamine secretion in bovine adrenal chromaffin cells. In addition to this action, the ginsenoside at higher concentrations modulates the fluidity of the plasma membrane, which probably contributes to the observed reduction in the secretion of catecholamines. (C) 2001 Elsevier Science Inc. All rights reserved.