Sy. Nah et al., A TRACE COMPONENT OF GINSENG THAT INHIBITS CA2-TOXIN-SENSITIVE G-PROTEIN( CHANNELS THROUGH A PERTUSSIS), Proceedings of the National Academy of Sciences of the United Statesof America, 92(19), 1995, pp. 8739-8743
A crude extract from ginseng root inhibits high-threshold, voltage dep
endent 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 ginseno
side 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 Rb
1, Rc, Re, and Rg1-caused relatively little inhibition of Ca2+ channel
s, and lipophilic components of ginseng root had no effect, Antagonist
s of a variety of neurotransmitter receptors that inhibit Ca2+ channel
s fail to alter the effect of Rf, raising the possibility that Rf acts
through another G protein-linked receptor. Rf also inhibits Ca2+ chan
nels in the hybrid F-11 cell line, which might, therefore, be useful f
or molecular characterization of the putative receptor for Rf. Because
it is not a peptide and it shares important cellular and molecular ta
rgets with opioids, Rf might be useful in itself or as a template for
designing additional modulators of neuronal Ca2+ channels.