RAT-LIVER CONTAINS A LIMITED NUMBER OF BINDING-SITES FOR HEPATIC LIPASE

The binding of hepatic lipase to rat liver was studied in an ex vivo p erfusion model. The livers were perfused with media containing partial ly purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the perfusion media before a nd after passage through the liver. During perfusion with a hepatic-li pase-containing medium the lipase activity in the medium did not chang e, indicating that there was no net binding of lipase by the liver. In contrast, more than 80% of the lipoprotein lipase was removed from th e medium. This lipoprotein lipase activity could be recovered into the perfusion medium completely by heparin perfusion of the liver. If liv ers, first depleted of hepatic lipase by heparin, were subsequent perf used with a hepatic-lipase-containing medium, 90+/-24 m-units of the l ipase activity was bound per g of liver (up to 1000 m-units/total live r). However, heparin treatment of the liver decreases the ability of t he liver to re-bind hepatic lipase by 80%. Perfusion of rat livers wit h 0.3 M NaCl released 60% of the lipase activity into the medium. Upon subsequent perfusion of these livers with hepatic-lipase-containing m edia, 541+/-164 m-units of hepatic lipase could be bound per g of live r (up to 5000 m-units/total liver). The binding of hepatic lipase was also studied in livers of corticotropin (ACTH)-pre-treated rats. In th ese rats also, hepatic lipase bound only to livers which had been pre- perfused with heparin or 0.3 M NaCl. After heparin pre-perfusion, 88+/ -12 m-units of hepatic Lipase could be bound per g of liver, similar t o that with livers of control rats not treated with ACTH. After prior salt perfusion, however, the capacity of the livers of ACTH-pre-treate d rats to bind hepatic lipase was 212+/-60 m-units/g of liver. This is less than in livers of control rats (541+/-164 m-units/g of liver). T hese results indicate that in rat liver the binding of hepatic lipase is heterogeneous in character and consists of heparin-resistant and he parin-sensitive components. The hepatic-lipase binding capacity of the liver is saturable and fully utilized under various conditions. The h eparin-sensitive binding capacity is lowered in ACTH-treated rats, whe reas the heparin-resistant binding is unaffected. We postulate that th e functional hepatic lipase activity can be regulated by changes in th e binding capacity of the liver.