Honokiol blocks store operated calcium entry in CHO cells expressing the M3 muscarinic receptor: honokiol and muscarinic signaling

Journal of Biomedical Science

Robert S Aronstam²  Ming-Huan Chan³  Yue-wern Huang²  Adam L Martin²  Rhett A Reichard²  Po-Kuan Chao¹  Alexis G Martin²  Hsiu-Jen Wang² 

[1] Department of Life Science, National Taiwan Normal University, 116, Taipei, Taiwan, R O C;Department of Biological Sciences, Missouri University of Science & Technology, 400 W. 11th St, Rolla MO 65409, USA;Institute of Neuroscience, National Chengchi University, Taipei, Taiwan

关键词: Phospholipase Cβ;    Muscarinic acetylcholine receptor;    Inositol trisphosphate (IP3);    Store operated calcium entry (SOCE);    Calcium signaling;    Honokiol;   

Others  :  824273
DOI  :  10.1186/1423-0127-20-11

 received in 2012-12-21, accepted in 2013-02-22,  发布年份 2013

【 摘 要 】

Background

Honokiol, a cell-permeable phenolic compound derived from the bark of magnolia trees and present in Asian herbal teas, has a unique array of pharmacological actions, including the inhibition of multiple autonomic responses. We determined the effects of honokiol on calcium signaling underlying transmission mediated by human M3 muscarinic receptors expressed in Chinese hamster ovary (CHO) cells. Receptor binding was determined in radiolabelled ligand binding assays; changes in intracellular calcium concentrations were determined using a fura-2 ratiometric imaging protocol; cytotoxicity was determined using a dye reduction assay.

Results

Honokiol had a potent (EC50 ≈ 5 μmol/l) inhibitory effect on store operated calcium entry (SOCE) that was induced by activation of the M3 receptors. This effect was specific, rapid and partially reversible, and was seen at concentrations not associated with cytotoxicity, inhibition of IP3 receptor-mediated calcium release, depletion of ER calcium stores, or disruption of M3 receptor binding.

Conclusions

It is likely that an inhibition of SOCE contributes to honokiol disruption of parasympathetic motor functions, as well as many of its beneficial pharmacological properties.

【 授权许可】

   
2013 Wang et al; licensee BioMed Central Ltd.

【 图 表 】

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