Inhibitory influence of ginsenoside Rb3 on activation of strychnine-sensitive glycine receptors in hippocampal neurons of rat

Whole-cell patch-clamp technique was used to investigate the effect of ginsenoside Rb-3 (Rb-3), an active constituent of Panax ginseng, on glycine receptor activity in immature hippocampal neurons, which were dissociated acutely from hippocampal CA, area in Sprague-Dawley rats aging 10-14 days using the method of enzyme digestion with mechanical dissociation. As a result, glycine elicited an inward current (I-gly) in a concentration-dependent manner in approximately 86% of those isolated neurons tested. This current was strychnine-sensitive. Rb-3 itself did not elicit any membrane currents. However, coapplication of Rb-3 inhibited peak current of I-gly. This depressant effect of Rb-3 varied with its concentrations. At a concentration of 0.1 mu mol/L, ginsenoside Rb-3 had the most significant inhibition, with a net reduction of 31% in average. Moreover, the inhibition of I-gly by Rb-3 did not depend on the membrane potential. Rb-3 (0.1 mu mol/L) presented inhibitory effect on Igly mainly at higher glycine concentrations (> 100 mu mol/L), and decreased maximal glycine efficacy. This effect was the same as that of a non-competitive antagonist of glycine receptors. Finally, we found that Rb-3 prolonged the time constant of activation of I-gly. It is therefore suggested that ginsenoside Rb-3, possibly as a non-competitive antagonist, could inhibit strychnine-sensitive glycine current at a dose-dependent manner in acutely dissociated hippocampal CA(1) neurons of young rats, and decrease of affinity of glycine to receptors and delay of receptor activation may be involved in this inhibition. Inhibitory effect of ginsenoside Rb-3 on I-gly is possibly one of the bases of many pharmacological actions of Panax ginseng. (c) 2005 Elsevier B.V. All rights reserved.