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Chrysin relaxes cholecystokinin or KCl‐induced tension in male guinea pig gallbladder strips through multiple signaling pathways
Author(s) -
Kline Loren,
Karpinski Edward
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1069.1
Subject(s) - chrysin , chemistry , cholecystokinin , muscle relaxation , genistein , endocrinology , protein kinase c , biophysics , medicine , pharmacology , biochemistry , signal transduction , biology , flavonoid , receptor , antioxidant
The flavonoids are a large group of plant‐derived phenolic compounds with biological effects including modulating vascular tone. The flavone, chrysin, has relaxant effects on vascular smooth muscle and intestinal smooth muscle. In this laboratory, chrysin relaxed cholecystokinin octapeptide (CCK) or KCl‐induced tension. The relaxation was concentration dependent. An in vitro technique was used to determine which second messenger system(s) mediate the observed relaxation. Paired t‐tests were used for statistical analysis. Differences between mean values with p<0.05 were considered significant. To determine if the PKA/cAMP second messenger system mediated the chrysin‐induced relaxation, PKA inhibitor 14–22 amide myristolated (PKA‐IM; 180 nM) was used. PKA‐IM caused a significant (p<0.001) decrease in chrysin‐induced relaxation (69.8±3.5 vs. 56.4±2.8%). When the PKC inhibitors bisindolymaleimide IV (0.5 μM) and chelerythrine Cl − (5 mM) were used together, a significant (p<0.01) reduction in chrysin‐induced relaxation (57.9±4.4 vs. 52.2±5.1%) was observed. 2‐APB (125 μM), an inhibitor of IP 3 induced intracellular Ca 2+ , significantly (p<0.001) decreased the amount of chrysin‐induced relaxation (60.7±6.0 vs. 49.1±2.5%). Genistein (10 μM), a protein tyrosine kinase inhibitor had no significant effect on the chrysin‐induced relaxation. L‐NMMA (20μM), a NO synthase inhibitor, had no significant effect on the amount of chrysin‐induced relaxation. The results show that the chrysin‐induced relaxation is mediated by the PKA/cAMP and PKC second messenger systems. The release of intracellular Ca 2+ is also involved in mediating the chrysin effect. Since chrysin also relaxed the KCl‐induced tension, extracellular Ca 2+ entry is also involved in mediating the chrysin‐induced relaxation. In conclusion, the chrysin‐induced relaxation is mediated by multiple signaling pathways.