CHARACTERIZATION OF PHLORETIN-SENSITIVE UREA EXPORT FROM THE PERFUSED-RAT-LIVER

In single pass perfused rat liver, rapid osmotic water shifts across t he plasma membrane in response to hyperosmolar urea were followed by m onitoring liver mass and transient concentrating or diluting effects o n Na+ concentration in effluent perfusate, Sudden addition or removal of hyperosmolar urea (200 mM, resulting in a step change of the perfus ate osmolarity from 305 to 505 mosmol/l) had little effect on liver ma ss or Na+ activity in the effluent perfusate, suggesting that urea equ ilibrated at a rate similar to that of water across the liver plasma m embrane. When, however, phloretin (0.2 mM) was present, sudden additio n (removal) of urea (200 mM) induced within seconds a marked and trans ient decrease (increase) of both liver mass and effluent Na+ concentra tion, suggestive of transient osmotic water shifts out of/into the cel ls, Although to a lesser extent, comparable effects were induced when urea was added/removed in the presence of the phloretin-related phenol compounds 2,4,6-trihydroxyacetophenone (5 mM) and 2,4,5-trihydroxybut yrophenone (5 mM), Phloretin-induced inhibition of urea export from li vers preloaded with [C-14]urea was reversible, and no saturation of ur ea transport was found at concentrations up to 200 mM. In contrast to [C-14]urea transport, [H-3] water transport across the plasma membrane was not affected by phloretin, The data indicate that urea export acr oss the hepatocyte plasma membrane is almost as fast as water export, The urea transport mechanism is sensitive to phloretin and other pheno l compounds, works with high capacity and is distinct from the water-t ransporting system, The regulation of this putative transport mechanis m and its relevance for hepatic nitrogen metabolism remain to be estab lished.