EXOCYTOTIC EXCRETION OF DEXTRAN SULFATES FROM LIVER TO BILE

Abstract

When dextran 35S-sulfates (DSs), anticoagulants and antilipemic agents, were intravenously given to rats, the specific radioactivity was five to twenty times higher in the lysosomal than in the other subcellular fractions of liver, but the counts in this fraction were only 10 % of total radioactivity distributed to the liver. Therefore, we investigated the biliary excretion of 35S-DSs with a similar sulfur content of 18% and three different average molecular weights (AMW) of 3000, 20,000, and 200,000. The excretion rate was about 2 % of the radioactivity given, per hour, after intravenous administration of 35S-DS with AMW of 20,000, 10 mg/kg. At this time, acid phosphatase activity and calcium content of bile also were increased, and well correlated with the amount of the radioactivity excreted to bile. The amount of the radioactivity distributed to the lysosomal fraction is correlated with the enhanced activities of Na+-K+-dependent and Ca2+-activated ATPase in this fraction, indexes of endocytotic and exocytotic transports. DSs significantly enhanced 45Ca levels of the lysosomal, but not the cytosol fraction when 45CaCl2 was given alone or simultaneously with DSs. According to our previous reports that DSs are transferred to the lysosomal fraction of liver and intestinal mucosa by endocytosis, the present results suggest that DSs, especially with high AMW and which are distributed to liver lysosomes are rapidly excreted into bile by exocytosis and accompanied by calcium and lysosomal enzymes.