Modulating effect of hydroxyacetophenones on hepato‐biliary excretion of horseradish peroxidase in rats

Vesicular transport as well as insertion of transporter protein into the canalicular membrane has currently been received as one of the key steps in choleretic mechanisms. In the present study, the possibility of involvement of hydroxyacetophenone analogs which differently exhibit choleretic activities on the biliary excretion of horseradish peroxidase (HRP), a marker of the transcytotic vesicle pathway was investigated using bile fistula rats. The analogs used include 4‐mono, 2,6‐di and 2,4,6‐tri hydroxy acetophenone (MHA, DHA and THA). MHA intra‐duodenally perfused which stimulated bile acid independent secretion (BAIF) showed a dose‐related increase in both early peak of paracellular and late peak of transcellular HRP excretion. THA which stimulated both bile acid dependent secretion (BADF) and BAIF did not alter the pattern of HRP excretion into bile. DHA which increased only BADF did not affect pattern of the early peak but caused a decrease in the late peak excretion. Colchicine‐pretreatment inhibited the stimulating effect of MHA on bile flow rate, suggesting that the choleretic action of MHA may involve the microtubule‐dependent transcytotic pathway, whereas the choleretic actions of THA and DHA did not associate with the vesicular transport. Detail of the different choleretic mechanism of hydroxyacetophenones in increase bile secretion from classic agents in mediating insertion of transporter via vesicular transport may offer a new method for developing choleretic agents (Supported by RGJ and Thailand Research Fund)