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Plasma membrane as the target site of cholic acid analogs

Archives of Pharmacal Research volume 34, Article number: 1153 (2011) Cite this article

Abstract

Although the mechanism is unknown, Calculus Bovis and its active components, cholic acid analogs (CAAs), have been used in China to treat a wide range of diseases. Based on the previous finding that the potency of CAA is strongly dependent on the intrinsic surface activity, this paper aimed to investigate the role of the plasma membrane in the pharmacological activity of CAAs. First, CAAs (0.1 mM) caused a surface activity-dependent depression on ATPase activity in the cell membrane extract, but it had no effects on other cellular extracts, suggesting an indispensable role of the membrane environment for pharmacological activity. Second, CAAs lowered the membrane fluidity of cultured Caco-2 cells with the same rank-order of potency sequence. Third, the hypothesis that any functional protein located on the membrane is influenced by changes in cellular membrane fluidity was supported by: ileal contraction that was induced by acetylcholine and mediated by the muscarinic receptor (M-receptor) or the relaxation induced by adrenaline and mediated by the β-adrenergic receptor (β-receptor) was inhibited by CAAs. They also had similar rank-order of potency and the effects on the plasma membrane. Collectively, the plasma membrane may be a target for the CAAs to exert the multiple pharmacological effects which are mediated by the alteration of the membrane mobility and the function of integral membrane proteins.

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References

  • Chen, X., Mellon, R. D., Yang, L., Dong, H., Oppenheim, J. J., and Howard, O. M., Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants. Biochem. Pharmacol., 63, 533–541 (2002).

    PubMed  Article  CAS  Google Scholar 

  • Dai, J., Chen, J., Han, B., Bei, Y., and Zhou, X., Regulation of calculus bovis on the function of mice oral fibroblasts. Sheng Wu Gong Cheng Xue Bao, 25, 448–451 (2009).

    PubMed  CAS  Google Scholar 

  • Greve, J. W., Gouma, D. J., and Buurman, W. A., Bile acids inhibit endotoxin-induced release of tumor necrosis factor by monocytes: an in vitro study. Hepatology, 10, 454–458 (1989).

    PubMed  Article  CAS  Google Scholar 

  • Hicks, R. M. and Ketterer, B., Isolation of the plasma membrane of the luminal surface of rat bladder epithelium, and the occurrence of a hexagonal lattice of subunits both in negatively stained whole mounts and in sectioned membranes. J. Cell Biol., 45, 542–553 (1970).

    PubMed  Article  CAS  Google Scholar 

  • Li, H., Lv, X., Ding, R., Zhang, T., Zhao, J., and Du, X., Effects of Ephedrine isomers and Cholic Acid Analogs, used alone or in combination, against histamine induced constriction of guinea pig tracheal in vitro. Chin. J. Med., 8, 1–5 (2008).

    Article  Google Scholar 

  • Li, Y. W., Zhu, X. Y., But, P. P., and Yeung, H. W., Ethnopharmacology of bear gall bladder: I. J. Ethnopharmacol., 47, 27–31 (1995).

    PubMed  Article  CAS  Google Scholar 

  • Lv, L., Liu, Y., Shi, H. F., and Dong, Q., Qingkailing injection attenuates apoptosis and neurologic deficits in a rat model of intracerebral hemorrhage. J. Ethnopharmacol., 125, 269–273 (2009).

    PubMed  Article  Google Scholar 

  • Mullineaux, C. W. and Kirchhoff, H., Using fluorescence recovery after photobleaching to measure lipid diffusion in membranes. Methods Mol. Biol., 400, 267–275 (2007).

    PubMed  Article  CAS  Google Scholar 

  • Zhang, S., Zhang, Y., Wang, W., Cao, X., Zhao, L., and Wang, J., The electrophysiological mechanism of relieving pain of calculus bovis sativus. Zhong Yao Tong Bao, 24, 1073–1077 (2008a).

    Google Scholar 

  • Zhang, T. H., Lin, J., Liu, C. G., Ding, R. G., Ruan, J. X., Sun, X. H., Huang, C. Q., and Zhang, X. C., Relationship between pharmacological potency and surface activity of cholic acid analogs. Int. J. Pharm., 4, 407–409 (2008b).

    Article  CAS  Google Scholar 

  • Zhao, Y. H. and Ruan, J. X., Pharmacology and clinical application of calculus bovis and its substitute. Chun Shih I Hsueh Ko Hsueh Yuan Yuan Kan, 31, 175–179 (2007).

    Google Scholar 

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Affiliations

  1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850, China

    Tian Hong Zhang, Zhen Qing Zhang & Jin Xiu Ruan

  2. Beijing Police Hospital, Beijing, 100027, China

    Chun Guang Liu

  3. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, 27 Taiping Road, Beijing, 100850, China

    Zhen Qing Zhang

Authors
  1. Tian Hong Zhang
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  2. Chun Guang Liu
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  3. Zhen Qing Zhang
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  4. Jin Xiu Ruan
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Correspondence to Zhen Qing Zhang.

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Zhang, T.H., Liu, C.G., Zhang, Z.Q. et al. Plasma membrane as the target site of cholic acid analogs. Arch. Pharm. Res. 34, 1153 (2011). https://doi.org/10.1007/s12272-011-0713-z

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  • DOI: https://doi.org/10.1007/s12272-011-0713-z

Key words

  • Calculus bovis
  • Cholic acid analogs
  • ATPase activity
  • Membrane fluidity
  • M- and β-receptor