Heparin and chondroitin sulfate inhibit adenine nucleotide hydrolysis in liver and kidney membrane enriched fractions

The inhibition of adenine nucleotide hydrolysis by heparin and chondroitin sulfate (sulfated polysaccharides) was studied in membrane preparations fro m liver and kidney of adult rats. Hydrolysis was measured by the activity o f NTPDase and 5'-nucleotidase. The inhibition of NTPDase by heparin was obs erved at three different pH values (6.0, 8.0 and 10.0). In liver, the maxim al inhibition observed for ATP and ADP hydrolysis was about 80% at pH 8.0 a nd 70% at pH 6.0 and 10.0. Similarly to the effect observed in liver, hepar in caused inhibition of ATP and ADP hydrolysis that reached a maximum of 70 % in kidney (pH 8.0). Na+, K+ and Rb+ changed the inhibitory potency of hep arin, suggesting that its effects may be related to charge interaction. In addition to heparin, chondroitin sulfate also caused a dose-dependent inhib ition in liver and kidney membranes. The maximal inhibition observed for AT P and ADP hydrolysis was about 60 and 50%, respectively. In addition, the h epatic and renal activity of 5'-nucleotidase was inhibited by heparin and c hondroitin sulfate, except for kidney membranes where chondroitin sulfate d id not alter AMP hydrolysis. On this basis. the findings indicate that glyc osaminoglycans have a potential role as inhibitors of adenine nucleotide hy drolysis on the surface of liver and kidney cell membranes in vitro. (C) 20 01 Elsevier Science Ltd. All rights reserved.