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.


Biological Sciences

Keywords and Phrases

Honokiol; Muscarinic M3 Receptor; Biphenyl Derivative; Calcium; Inositol 1,4,5 Trisphosphate; Animal Cell; Binding Assay; Calcium Signaling; Calcium Transport; Cell Viability; Cytotoxicity; Cytotoxicity Test; Drug Effect; IC 50; Ligand Binding; Nonhuman; Receptor Binding; Cytoplasm; Gene Expression Regulation; Hamster; Ion Transport; Metabolism; Cricetulus griseus; Magnolia; Animals; Biphenyl Compounds; Calcium Signaling; CHO Cells; Cricetinae; Humans; Lignans; Receptor, Muscarinic M3; Inositol Trisphosphate (IP3); Muscarinic Acetylcholine Receptor; Phospholipase C[beta]; Store Operated Calcium Entry (SOCE)

International Standard Serial Number (ISSN)

1021-7770; 1423-0127

Document Type

Article - Journal

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Final Version

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This work is licensed under a Creative Commons Attribution 2.0 License.

Publication Date

01 Feb 2013

PubMed ID


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