The effects of synthetic prostaglandin analogs on canine hepatic bile flow

Abstract

The synthetic prostaglandin analogs 16, 16-dimethyl PGF 2α and 16, 16-dimethyl PGE 2 were administered to dogs with chronic biliary and gastric fistulas. The effects of 16, 16 diMePGF 2α and 16, 16 diMePGE 2 were evaluated on bile flow and composition and bile adenosine 3′, 5′ monophosphate (cyclic AMP) secretion. 16, 16 diMePGF 2α in doses of 0.125 and 0.25 μg-kg-min significantly increased hepatic bile flow. The choleresis was characterized by increased cloride 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 diMePGF 2α. The administration of 16, 16 diMePGE 2 in a dose range 0.01 to 1.0 μg-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 PGF 2α but not by 16, 16-dimethyl PGF 2α, suggesting that the mechanism of action of PGF 2α in stimulating hepatic bile flow may be different from that involved in 16, 16-dimethyl PGF 2α choleresis. The results of this study indicate that the synthetic PGF 2α analog produces a choleretic response not mediated by adenylate cyclase and associated with increased chloride and bicarbonate secretion.