title: Honokiol blocks store operated calcium entry in CHO cells expressing the M3 muscarinic receptor: honokiol and muscarinic signaling.
abstract: 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.
authors: Department of Biological Sciences, Missouri University of Science & Technology, 400 W, 11th St, Rolla MO 65409, USA.
authors: Hsiu-Jen
authors: HJ
authors: Wang
authors: Alexis G
authors: AG
authors: Martin
authors: Po-Kuan
authors: PK
authors: Chao
authors: Rhett A
authors: RA
authors: Reichard
authors: Adam L
authors: AL
authors: Martin
authors: Yue-wern
authors: YW
authors: Huang
authors: Ming-Huan
authors: MH
authors: Chan
authors: Robert S
authors: RS
authors: Aronstam
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D006224:Cricetinae; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D017705:Lignans / Q000008:administration & dosage*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D001713:Biphenyl Compounds; D002118:Calcium; D015544:Inositol 1,4,5-Trisphosphate; D017705:Lignans; D043587:Receptor, Muscarinic M3; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols