Effect of suramin on the activities of degradative enzymes of sphingolipids in rats.
Three to nine days after administration of suramin, 500 mg/kg intravenously in rats, a small amount of the drug (about 0.25 micromoles/g tissue) was retained by the liver and spleen, and a larger amount (about 1.2 micromoles/g tissue) was retained by the kidneys. The activities of the sphingolipid hydrolases beta-hexosaminidase and GM3-sialidase were strongly inhibited by suramin in vitro. The activity of beta-hexosaminidase was inhibited 70% by 10(-5M) and 85% by 10(-4M) suramin, and the activity of GM3-sialidase was inhibited 80% by 10(-4M) suramin. The activities of sphingomyelinase and beta-galactosidase were also inhibited by suramin but at higher concentrations of the drug. Suramin, in vitro is a weak inhibitor of glucocerebrosidase, galactocerebrosidase, alpha-galactosidase and arylsulfatase A (less than 50% inhibition at 10(-3M) concentration of the drug). The inhibition of beta-hexosaminidase by suramin was non-competitive. Inhibition of beta-hexosaminidase and GM3-sialidase may explain the accumulation of GM2 and GM3 gangliosides in the brains of rats treated intracerebrally with suramin (Constantopoulos et al, 1980).
D000818:Animals; D006596:Hexosaminidases / Q000037:antagonists & inhibitors; D066298:In Vitro Techniques; D008247:Lysosomes / Q000201:enzymology; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D051381:Rats; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000032:analysis; D013498:Suramin / Q000378:metabolism / Q000494:pharmacology*
D013107:Sphingolipids; D013498:Suramin; D013108:Sphingomyelin Phosphodiesterase; D006596:Hexosaminidases; D009439:Neuraminidase