title: The Resveratrol-induced Relaxation of Cholecystokinin Octapeptide- or KCl-induced Tension in Male Guinea Pig Gallbladder Strips Is Mediated Through L-type Ca2+Channels.
abstract: OBJECTIVE
  Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenolic compound (stilbene) and a phytoalexin. The purpose of this study was to determine the mechanism which mediated the resveratrol-induced relaxation of cholecystokinin octapeptide- or KCl-induced tension in male guinea pig gallbladder strips.
  
  
  METHODS
  Gallbladder strips were prepared and suspended in in vitro chambers filled with Krebs-Henseleit solution. The strips were attached to force displacement transducers, and the changes in tension were recorded on a polygraph. All reagents were added directly into the chambers.
  
  
  RESULTS
  To determine if intracellular Ca(2+) release mediated the resveratrol-induced relaxation of cholecystokinin octapeptide-induced tension, 2-aminoethoxydiphenylborane (2-APB) was used. 2-APB significantly (P < 0.01) decreased the amount of RSVL-induced relaxation. To determine if protein kinase A (PKA) mediated the resveratrol-induced relaxation, PKA inhibitor 14-22 amide myristolated (PKA-IM) was used. PKA-IM had no effect on resveratrol-induced relaxation. Neither KT5823, N(G)-methyl-L-arginine acetate salt, a nitric oxide synthase inhibitor, nor fulvestrant had a significant effect on the amount of resveratrol-induced relaxation. Genistein, a protein tyrosine kinase inhibitor, significantly (P < 0.01) increased the RSVL-induced relaxation. To determine if protein kinase C mediated the RSVL-induced relaxation, the protein kinase C inhibitors bisindolymaleimide IV and chelerythrine Cl- were used together, and a significant (P < 0.05) increase in resveratrol-induced relaxation was observed. The pretreatment of the strips with resveratrol significantly (P < 0.001) decreased the amount of KCl- and cholecystokinin octapeptide- induced tension.
  
  
  CONCLUSIONS
  Resveratrol-induced relaxation is mediated by its effects on L-type Ca(2+) channels and intracellular Ca(2+) release.
authors.affiliation: Departments of Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Loren W
authors.initials: LW
authors.lastname: Kline
authors.affiliation: Departments of Physiology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Karpinski
keywords: Calcium channels; Gallbladder; Muscle, smooth; Phytoalexins; Resveratrol