title: Curcumin Relaxes Precontracted Guinea Pig Gallbladder Strips via Multiple Signaling Pathways.
abstract: BACKGROUND
  Curcumin (diferuloymethane) is the active ingredient of the dietary spice turmeric. Curcumin modulates various signalling molecules, including inflammatory agents, transcription factors, protein kinases and cell cycle regulatory proteins. The purpose of this study was to determine if curcumin had an effect on gallbladder motility.
  
  
  METHODS
  A pharmacologicin vitrotechnique was used. Since curcumin relaxed both cholecystokinin octapeptide- (CCK) and KCl-induced tension of guinea pig gallbladder strips in a concentration dependent manner, anin vitrotechnique was used to determine which second messenger system(s) mediated the observed relaxation. Pairedt-tests,t-tests and analysis of variance were used for statistical analysis. Differences between mean values of P < 0.05 were considered significant.
  
  
  RESULTS
  To determine if protein kinase A (PKA) mediated the curcumin-induced relaxation, PKA inhibitor 14-22 amide myristolated (PKA-IM) was used. PKA-IM had no significant effect on the amount of curcumin-induced relaxation. When the protein kinase C (PKC) inhibitors bisindolymaleimide IV and chelerythrine Cl-were used together, a significant (P < 0.01) reduction in the curcumin-induced relaxation was observed. The use of tetraethylammonium chloride (TEA) caused a significant (P < 0.01) decrease in the amount of curcumin-induced relaxation. Adding curcumin prior to the KCl caused a significant (P < 0.001) decrease in the amount of KCl-induced tension.
  
  
  CONCLUSIONS
  The results suggested that the curcumin-induced relaxation is mediated by multiple signaling pathways including the PKC second messenger system, inhibiting extracellular Ca2+entry and K+ channels.
authors: School of Dentistry, University of Alberta, Edmonton, Alberta T6G 2E1, Canada.
authors: Loren W
authors: LW
authors: Kline
authors: Department of Physiology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
authors: Edward
authors: E
authors: Karpinski
keywords: Calcium channels; Curcumin; Gallbladder; Potassium channels; Smooth muscle