Curcumin stimulates cystic fibrosis transmembrane conductance regulator Cl- channel activity.
Compounds that enhance either the function or biosynthetic processing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel may be of value in developing new treatments for cystic fibrosis (CF). Previous studies suggested that the herbal extract curcumin might affect the processing of a common CF mutant, CFTR-DeltaF508. Here, we tested the hypothesis that curcumin influences channel function. Curcumin increased CFTR channel activity in excised, inside-out membrane patches by reducing channel closed time and prolonging the time channels remained open. Stimulation was dose-dependent, reversible, and greater than that observed with genistein, another compound that stimulates CFTR. Curcumin-dependent stimulation required phosphorylated channels and the presence of ATP. We found that curcumin increased the activity of both wild-type and DeltaF508 channels. Adding curcumin also increased Cl(-) transport in differentiated non-CF airway epithelia but not in CF epithelia. These results suggest that curcumin may directly stimulate CFTR Cl(-) channels.
Berger
Allan L
AL
Department of Internal Medicine, Howard Hughes Medical Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Randak
Christoph O
CO
Ostedgaard
Lynda S
LS
Karp
Philip H
PH
Vermeer
Daniel W
DW
Welsh
Michael J
MJ
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D017384:Sequence Deletion / Q000235:genetics
C505032:CFTR protein, human; D002712:Chlorides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D019833:Genistein; D017868:Cyclic AMP-Dependent Protein Kinases; D003474:Curcumin