The effects of 1,7-bis( p-aminophenoxy)heptane (153C51) on glucose utilization by Schistosoma mansoni

Abstract

1. There was no consistent change in glycogenolysis in S. mansoni males and females incubated together in vitro 24 hr after treatment of the host with a therapeutic dose of 153C51. 2. In similar incubations, glycolysis was significantly reduced only when the lowest concentration of glucose (0.4 mM) was added to the medium. 3. Experiments on the uptake of 0.5 mM D-[U- 14C] glucose and the non-metabolized analogue 2-deoxy- D-[1- 3H] glucose by pairs and by male and female schistosomes incubated separately indicated that the inhibition of utilization of glucose from low substrate concentration in males and females incubated together could be explained by an inhibition of glucose uptake in male worms. Uptake by female worms was unaffected by drug treatment. 4. The rapid accumulation of radioactivity derived from 1.7-bis( p-aminophenoxy)[1.7- 14C]heptane preceded the onset of inhibition of 2DOG uptake by male parasites by several hours. Throughout the period 1–24 hr after treatment of the host, female schistosomes were approximately 50% more radioactive than males yet in this study they were almost totally unaffected by the drug. 5. The accumulation by schistosomes of radioactivity derived from 153C51 labelled in different positions accords with earlier work on the basic chemical structure essential for schistosomicidal activity in this type of compound. 6. The similarity in the glycogen reserves of pairs of control parasites and those pairs removed from treated mice together with the results of the experiments on glucose utilization in vitro make it unlikely that the interference with glucose uptake observed in vitro in male parasites could be a primary cause of schistosome death or even of physiological distress in 153C51-treated parasites in vivo.