[A study on the mechanism of the choleretic effect of proglumide]

It has been found in this laboratory that proglumide (PGM) can increase hepatic bile flow in humans and in several species of animals, and lower gallstone formation in experimental animals. In order to further investigate the mechanisms of this choleretic effect of PGM, studies with isolated rat liver cells and plasma membranes were performed. The results indicated that PGM could increase the activity of membrane Na+, K(+)-ATPase significantly. On the other hand, PGM decreased the net uptake of 14C-glycocholic acid by rat liver cells. These data suggest that the choleretic effect of PGM is likely to be mediated through the enhancement of membrane Na+, K(+)-ATPase activity (which would in turn increase water and electrolyte output), rather than by affecting bile acid uptake by liver cells. It was also observed that PGM could reverse the inhibitory effect of somatostatin on the activity of membrane Na+, K(+)-ATPase. These results provide some clues for the elucidation of the mechanisms of the inhibitory effect of PGM on gallstone formation in experimental animals.