Effect of proglumide on choleresis in rats

We are the first to report that proglumide (PGM) has a marked effect on promoting choleresis in rats. After iv infusion PGM 50, 100, 200, 400 mg/(kg.h), the bile quantities of 120-150 min were 0.4 +/- 0.14, 0.46 +/- 0.11, 0.75 +/- 0.25, 0.87 +/- 0.21 ml/30 min, respectively. They were significantly higher values than either basic bile flow (0.24 +/- 0.06 ml/30 min) or the solvent control of 5% NaHCO3 (0.22 +/- 0.13 ml/30 min, P less than 0.01) and obviously dose-dependent. After ig PGM 200 mg, bile flow observed at the peak of secretion between 60-90 min was 0.67 +/- 0.22 ml/30 min. Compared to that observed before PGM administration, the bile fluid collected was found to have increased 1.7-3.2 times, up to even 7 times. The choleretic effect continued 8-12 h after the infusion was terminated. The secretions of HCO3- and chlorides in the bile also increased during PGM infusion as compared with the control (P less than 0.05-0.01). On the contrary, the concentrations of cholic acids decreased remarkably (P less than 0.05-0.01). It is suggested that the mechanism of choleresis promoted by the infusion of PGM may be cholic acid-independent, but that it is related to the secretion of inorganic salts in cholangiole. Compared with three other choleretics commonly used clinically, phenylpropanol, dehydrocholic acid and sodium taurocholate, the effect of PGM is significantly superior (P less than 0.01).