A TRACE COMPONENT OF GINSENG THAT INHIBITS CA2+ CHANNELS THROUGH A PERTUSSIS-TOXIN-SENSITIVE G-PROTEIN

A crude extract from ginseng root inhibits high-threshold, voltage dependent Ca2+ channels through an unknown receptor linked to a pertussis toxin-sensitive G protein. We now have found the particular compound that seems responsible far the effect: it is a saponin, called ginsenoside Rf(Rf), that is present in only trace amounts within ginseng. At saturating concentrations, Rf rapidly and reversibly inhibits N-type, and other high-threshold, Ca2+ channels in rat sensory neurons to the same degree as a maximal dose of opioids. The effect is dose-dependent (half-maximal inhibition: 40 mu M) and it is virtually eliminated by pretreatment of the neurons with pertussis toxin, an inhibitor of G(o) and G(i) GTP-binding proteins, Other ginseng saponins-ginsenosides Rb1, Rc, Re, and Rg1-caused relatively little inhibition of Ca2+ channels, and lipophilic components of ginseng root had no effect, Antagonists of a variety of neurotransmitter receptors that inhibit Ca2+ channels fail to alter the effect of Rf, raising the possibility that Rf acts through another G protein-linked receptor. Rf also inhibits Ca2+ channels in the hybrid F-11 cell line, which might, therefore, be useful for molecular characterization of the putative receptor for Rf. Because it is not a peptide and it shares important cellular and molecular targets with opioids, Rf might be useful in itself or as a template for designing additional modulators of neuronal Ca2+ channels.