Ginsenoside-Rd from panax notoginseng blocks Ca2+ influx through receptor- and store-operated Ca2+ channels in vascular smooth muscle cells.

Previously, it was found that total saponins from panax notoginseng inhibited Ca2+ influx coupling to activation of alpha1-adrenoceptor. This study was designed to investigate the effects of ginsenoside-Rd from total saponins of panax notoginseng on receptor-operated (ROCC) and store-operated (SOCC) Ca2+ channels in vascular smooth muscle cells using fura-2 fluorescence, whole cell patch clamp ion channel recording, radio-ligand-receptor binding, 45Ca2+ radio-trace and organ bath techniques. It was found that ginsenoside-Rd reduced phenylephrine-induced contractile responses and Ca2+ influx in normal media without significant effect on these responses in Ca2+ -free media. Ginsenoside-Rd also decreased phenylephrine- and thapsigargin-induced inward Ca2+ currents, and attenuated thapsigargin- and 1-oleoy-2-acetyl-sn-glycerol (OAG)-induced cation entries that are coupled to ROCC and SOCC respectively. Ginsenoside-Rd failed to inhibit KCl-induced contraction of rat aortal rings and Ca2+ influx, and did not alter voltage-dependent inward Ca2+ current (VDCC) which was blocked by nifedipine. Also, ginsenoside-Rd did not change binding site and affinity of [3H]-prazosin for alpha1-adrenoceptor in the vascular plasma membrane. These results suggest that ginsenoside-Rd, as an inhibitor, remarkably inhibits Ca2+ entry through ROCC and SOCC without effects on VDCC and Ca2+ release in vascular smooth muscle cells.