The Flavone Luteolin, an Endocrine Disruptor, Relaxed Male Guinea Pig Gallbladder Strips

摘要

Background: Luteolin (3',4',5,7-tetrahydroxyflavone) is a flavone with a yellow crystalline appearance present in numerous plants such as broccoli, green chili, and carrot. Luteolin is considered to be an endocrine disruptor with potent estrogen agonist activity and potent progesterone antagonist activity. Luteolin has effects on smooth muscle. Luteolin relaxed guinea pig trachea smooth muscle as it inhibited both phosphodiesterase and reduced intracellular Casup2+/sup. Luteolin also caused vasorelaxation in rat thoracic aorta smooth muscle by inhibiting intracellular Casup2+/sup release, inhibition of sarcolemmal Casup2+/sup channels, and activation of Ksup+/sup channels. Luteolin or its glycosides from artichoke extracts may have an ameliorating effect on irritable bowel syndrome. The purpose of this study was to determine if luteolin had an effect on gallbladder motility. Methods: An in vitro pharmacologic technique was utilized. Either cholecystokinin octapeptide (CCK) or KCl were used to induce tension in male guinea pig gallbladder strips maintained in Sawyer-Bartlestone chambers. Luteolin relaxed either the CCK- or KCl-induced tension in a concentration dependent manner. Various blockers were added to the chambers to determine which second messenger system(s) mediated the observed relaxation. Paired t -tests were used for statistical analysis. Differences between mean values of P 0.05 were considered significant. Results: Treatment of the gallbladder strips with luteolin prior to either KCl or CCK significantly (P 0.001) decreased the amount of either KCl- or cholecystokinin-induced tension. The 2-aminoethoxydiphenylborane was used to ascertain if the release of intracellular Casup2+/sup mediated the luteolin-induced relaxation. It significantly (P 0.001) decreased the amount of luteolin-induced relaxation. To ascertain if PKA mediated the luteolin-induced relaxation, PKA inhibitor 14-22 amide myristolated was used. It significantly (P 0.01) reduced the amount of luteolin-induced relaxation. Neither KT5823, NsupG/sup-methyl-L-arginine acetate salt, genistein, tetraethylammonium, nor fulvestrant had a significant effect. To ascertain if PKC mediated the luteolin-induced relaxation, the PKC inhibitors bisindolymaleimide IV and chelerythrine Clsup-/sup were used together. They had no significant effect. Conclusions: Luteolin relaxed cholecystokinin- or KCl-induced tension by blocking extracellular Casup2+/sup entry as well as intracellular Casup2+/sup release. In addition, the actions of PKA are also involved in mediating the luteolin effect.