J Neurogastroenterol Motil.  2015 Jan;21(1):62-68. 10.5056/jnm14093.

The Resveratrol-induced Relaxation of Cholecystokinin Octapeptide- or KCl-induced Tension in Male Guinea Pig Gallbladder Strips Is Mediated Through L-type Ca2+ Channels

• Kline LW
• Karpinski

• KMID: 2381232
• DOI: http://doi.org/10.5056/jnm14093

Abstract

BACKGROUND/AIMS
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 Ca2+ 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 octapep-tide-induced tension.
CONCLUSIONS
Resveratrol-induced relaxation is mediated by its effects on L-type Ca2+ channels and intracellular Ca2+ release.

Keyword

Calcium channels; Gallbladder; Muscle, smooth; Phytoalexins; Resveratrol

MeSH Terms

Animals
Calcium Channels
Cholecystokinin*
Cyclic AMP-Dependent Protein Kinases
Gallbladder*
Genistein
Guinea Pigs*
Humans
Indicators and Reagents
Male
Muscle, Smooth
Nitric Oxide Synthase
Protein Kinase C
Protein-Tyrosine Kinases
Relaxation*
Transducers
Calcium Channels
Cholecystokinin
Cyclic AMP-Dependent Protein Kinases
Genistein
Indicators and Reagents
Nitric Oxide Synthase
Protein Kinase C
Protein-Tyrosine Kinases