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 Ca2+. Luteolin 
also caused vasorelaxation in rat thoracic aorta smooth muscle by inhibiting 
intracellular Ca2+ release, inhibition of sarcolemmal Ca2+ channels, and 
activation of K+ 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 Ca2+ 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, 
NG-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 Cl- were used together. They had no significant effect.
CONCLUSIONS: Luteolin relaxed cholecystokinin- or KCl-induced tension by 
blocking extracellular Ca2+ entry as well as intracellular Ca2+ release. In 
addition, the actions of PKA are also involved in mediating the luteolin effect.