The flavonoid chrysin, an endocrine disrupter, relaxes cholecystokinin- and KCl-induced tension in male guinea pig gallbladder strips through multiple signaling pathways

• Chrysin relaxed guinea pig gallbladder strips in a concentration dependent manner.
• The PKA/cAMP second messenger system mediates part of the relaxation.
• The PKC second messenger system mediates part of the relaxation.
• Inhibition of extracellular Ca2+ entry mediated part of the relaxation.
• Inhibition of intracellular Ca2+ release mediated part of the relaxation.

The bioflavonoids have effects on vascular smooth muscle and gastrointestinal smooth muscle. The flavone and phytoestrogen, chrysin, has been shown to have a vasorelaxant effect on resistance blood vessels. This effect was mediated by nitric oxide (NO). Chrysin inhibited aromatase/estrogen biosynthesis in postmenopausal women. The purpose of this study was to determine if chrysin had an effect on cholecystokinin- or KCl-induced tension in male guinea pig gallbladder strips. In addition, the second messenger(s) system(s) that mediated the effect were to be determined. A pharmacologic approach was used. Male guinea pig gallbladder strips were placed in in vitro chambers filled with Krebs solution, maintained at 37 °C, and gassed with 95% O2–5% CO2. Changes in tension were recorded using a polygraph.It was shown that the PKA/cAMP second messenger system mediated part of the observed chrysin-induced relaxation of cholecystokinin-induced tension, the PKC system also mediated part of the relaxation, and the inhibition of both extracellular Ca2+ entry and intracellular Ca2+ release also mediated the chrysin-induced relaxation. This is the first report of chrysin having an effect on gallbladder smooth muscle contraction.

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