Distinctive effect of ginseng saponins on development of morphine tolerance in guinea-pig ileum and mouse vas deferens.

Studies on the effect of ginseng saponins on the development of tolerance to morphine have been carried out using isolated preparations of guinea-pig ileum (GPI) and mouse vas deferens (MVD). Incubation of GPI preparation with morphine resulted in the development of tolerance to the inhibitory effect of morphine on the electrically evoked contractions. Ginseng total saponins and one of the constituents, protopanaxatriol saponin, suppressed the development of morphine tolerance in a concentration dependent manner in GPI preparation, though another constituent, protopanaxadiol saponin, did not affect the tolerance development substantially. In the MVD preparation, the development of tolerance to the morphine effect was observed as well, but none of the ginseng saponins affected it. It has been well established that electrically evoked contractions of GPI and MVD are mediated by acetylcholine and norepinephrine, respectively, and presumably their release is regulated presynaptically by opioid receptors. The fact that ginseng saponins suppressed the development of morphine tolerance only in the GPI preparation suggest that the inhibitory effect is mediated through and effect on the cholinergic system, without the involvement of direct action on opioid receptors.