Abstract

Dihydroxydibutyl ether (DDE) induces a choleresis and a diuresis in the rat. The stimulation of bile flow is immediate and dose-dependent; DDE appears to stimulate bile acid-independent flow of canalicular origin, because erythritol clearance increased in parallel to bile flow and choleresis occurs in the absence of an increased bile acid secretion. Increased bile flow may be accounted for by the osmotic activity of DDE and DDE metabolites excreted into bile, with an average increase in bile flow of 16 microliters/mumol of DDE (or DDE metabolites). Biliary secretion of DDE is limited with a maximal rate (biliary Tm) of 773 nmol.min-1.100 g b.wt.-1. The metabolic products of DDE in bile appear to be its mono- and diglucuronide conjugates inasmuch as DDE can be recovered after beta-glucuronidase incubation. DDE and a DDE glucuronide conjugate are also detected in the urine: there is an apparently linear relation between DDE (and DDE metabolites) excretion rate and increase in urinary flow (3.5 microliters/mumol of DDE or DDE metabolites). It is concluded that DDE stimulates choleresis and diuresis in the rat because the molecule and its glucuronide conjugates are secreted and concentrated in bile and urine.