Transport and metabolism of dextran sulfates and the effect of calcium

Japanese Journal of Pharmacology

1980

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Abstract-When dextran "S-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 of35S-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 Nat-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.Macromolecules can enter into cells (1-3). DeDuve and Wattiaux (4) reported that dextran, a high molecular weight polysaccharide, is transported to liver cells and accumulates within endocytotic granules in the cytosol. Most of the granules can be collected in the lysosomal fraction by subcellular fractionation (5). Aronson and Davidson (6) and our group (7) have indicated that acid polysaccharides, chondroitin sulfates and dextran sulfates (DSs), are found in the lysosomal fraction of rat liver after intravenous administration.When 35S-labeled DS with an average molecular weight of 200,000 was given intraduodenally, the lysosomal fraction of intestinal mucosa contained 40 % of the tissue radioactivity (8). In the liver lysosomal fraction only 10 % of the tissue radioactivity was found after intravenous administration of the DS (7).Acid polysaccharides distributed to liver lysosomes are eliminated by catabolism (6) and biliary excretion. DeDuve and Wattiaux (4) indicated that dextran which was transferred to liver lysosomes is rapidly excreted to bile. Therefore, the difference in lysosome/ tissue ratio of the radioactivity between liver and intestinal mucosa may be due to the rapid biliary excretion of 35S-DSs distributed to liver lysosomes. Thus, we examined the biliary excretion of DSs with a similar sulfur content of 18 % and three different average molecular weights of 3000, 20,000, and 200,000. Our findings are reported herein.

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mentioning

confidence: 99%

Exocytotic Excretion of Dextran Sulfates From Liver to Bile

Japanese Journal of Pharmacology

1980

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“…In a previous report (3) we showed that, when a heparinoid having strong anticoagulant and antilipemic activities, 35S-DS with average molecular weight of 200,000 and sulfur content of 18 %, was given intraduodenally, large amounts of the radioactivity were found in the bile, the concentration being twice that found in the blood. Therefore, it may be that DSs are eliminated from circulation by two routes, via kidneys and liver.…”

mentioning

confidence: 89%

Transport of dextran sulfates to rat livers.

1979

Jpn.J.Pharmacol

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Abstract-Liver subcellular distributions of three different dextran sulfates (DSs) with average molecular weight (AMW) of 3000, 20,000 and 200,000, and sulfur content of 18 %, anticoagulants and antilipemic agents, were examined in rats after intravenous administration of 50 mg/kg. About 20 % of the injected radioactivity was taken up by liver 15 min-3 hr after 35S-DS administration, but the uptake of 35S-DS with AMW of 200,000 was slower tha., that of the other DSs. About half of the radioactivity distributed in livers was fot...d in the cytosol fraction.The cytosol fraction/liver ratio of the radioactivity gradually decreased with the increase in the nuclear fraction/liver ratio. The specific radioactivity of the lysosomal fraction was 5-20 times as large as that of the other fractions.Unchanged forms of 35S-DSs with AMW of 3000 and 20,000 were found in the lysosomal and the cytosol fractions.Administration of DSs with AMW of 20,000 and 200,000 significantly enhanced the Na+-K+-dependent ATPase activity of lysosomal fraction which has been considered to be an index of endocytosis. These findings suggest that DSs are probably transferred into liver cells by transmembrane and endocytotic transports.Heparin given i.v. in high doses is distributed into the extracellular spaces (1). Kaplan and Meyer (2) reported that chondroitin sulfates were excreted mainly into the urine. Thus, acid polysaccharides may rapidly distribute to extracellular spaces and be excreted into the urine. The mechanism of the transport into cells has, however, not been elucidated.In a previous report (3) we showed that, when a heparinoid having strong anticoagulant and antilipemic activities, 35S-DS with average molecular weight of 200,000 and sulfur content of 18 %, was given intraduodenally, large amounts of the radioactivity were found

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Activation of calcium-ATPase of liver plasma membrane by dextran sulfates

Biochemical and Biophysical Research Communications

1979