Abstract
We previously demonstrated the ability of ginseng saponins (active ingredients ofPanax ginseng) to enhance Ca2+-activated Cl∼ current. The mechanism for this ginseng saponin-induced enhancement was proposed to be the release of Ca2+ from IP3-sensitive intracellular stores through the activation of PTX-insensitive Gαa/11, proteins and PLC pathway. Recent studies have shown that calmodulin (CaM) regulates IP3 receptor-mediated Ca2+ release in both Ca2+-dependent and -independent manner. In the present study, we have investigated the effects of CaM on ginseng saponin-induced Ca2+-activated CI-current responses inXenopus oocytes. Intraoocyte injection of CaM inhibited ginseng saponin-induced Ca2+-activated CI-current enhancement, whereas co-injection of calmidazolium, a CaM antagonist, with CaM blocked CaM action. The inhibitory effect of CaM on ginseng saponin-induced Ca2+-activated CI-current enhancement was dose- and time-dependent, with an IC50 of 14.9 ± 3.5 μM. The inhibitory effect of CaM on saponin’s activity was maximal after 6 h of intraoocyte injection of CaM, and after 48 h the activity of saponin recovered to control level. The half-recovery time was calculated to be 16.7 ± 4.3 h. Intraoocyte injection of CaM inhibited Ca2+-induced Ca2+-activated CI-current enhancement and also attenuated IP3-induced Ca2+-activated CI-current enhancement. Ca2+/CaM kinase II inhibitor did not inhibit CaM-caused attenuation of ginseng saponin-induced Ca2+-activated CI-current enhancement. These results suggest that CaM regulates ginseng saponin effect on Ca2+-activated CI-current enhancementvia Ca2+-independent manner.
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Lee, JH., Jeong, SM., Lee, BH. et al. Effect of calmodulin on ginseng saponin-induced Ca2+-Activated CI-channel activation inXenopus laevis oocytes. Arch Pharm Res 28, 413–420 (2005). https://doi.org/10.1007/BF02977670
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DOI: https://doi.org/10.1007/BF02977670