The effects of synthetic prostaglandin analogs on canine hepatic bile flow.

The synthetic prostaglandin analogs 16, 16-dimethyl PGF2 alpha and 16, 16-dimethyl PGE2 were administered to dogs with chronic biliary and gastric fistulas. The effects of 16, 16 diMePGF2 alpha and 16, 16 diMePGE2 were evaluated on bile flow and composition and bile adenosine 3', 5' monophosphate (cyclic AMP) secretion. 16, 16 diMePGF2 alpha in doses of 0.125 and 0.25 microgram-kg-min significantly increased hepatic bile flow. The choleresis was characterized by increased chloride and bicarbonate secretion. Measurement by radioimmunoassay of bile cyclic AMP concentration demonstrated no evident increase in bile cyclic AMP secretion associated with the choleresis produced by 16, 16 diMePGF2 alpha. The administration of 16, 16 diMePGE2 in a dose range 0.01 to 1.0 microgram-kg-min did not significantly alter bile flow rates or composition. Bile erythritol-14C clearance, a measure of canalicular bile flow, was significantly increased by PGF2 alpha but not by 16, 16-dimethyl PGF2 alpha, suggesting that the mechanism of action of PGF2 alpha in stimulating hepatic bile flow may be different from that involved in 16, 16-dimethyl PGF2 alpha choleresis. The results of this study indicate that the synthetic PGF2 alpha analog produces a choleretic response not mediated by adenylate cyclase and associated with increased chloride and bicarbonate secretion.