EFFECT OF SURAMIN ON THE ACTIVITIES OF DEGRADATIVE ENZYMES OF SPHINGOLIPIDS IN RATS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 32  (1) , 87-97
Abstract
Three to 9 days after administration of suramin a trypanocidal agent, 500 mg/kg i.v. in rats, a small amount of the drug (about 0.25 .mu.mol/g tissue) was retained by the liver and spleen, and a larger amount (about 1.2 .mu.mol/g tissue) was retained by the kidneys. The activities of the sphingolipid hydrolases .beta.-hexosaminidase and ganglioside M3 [GM3]-sialidase were strongly inhibited by suramin in vitro. The activity of .beta.-hexosaminidase was inhibted 70% by 10-5 M and 85% by 10-4 M suramin, and the activity of GM3-sialidase was inhibted 80% by 10-4 M suramin. The activities of sphingomyelinase and .beta.-galactosidase were also inhibted 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 10-3 M concentration of the drug). The inhibition of .beta.-hexosaminidase by suramin was non-competitive. Inhibition of .beta.-hexosaimindase and GM3-sialidase may explain the accumulation of ganglioside M2 and GM3 gangliosides in the brains of rats treated intracerebrally with suramin.