Cerebral lysosomes. VI. The in vivo uptake of Triton-WR-1339 by the lysosomes of the immature cerebral cortex and cerebellum

Abstract

The detergent Triton-WR-1339 was injected intrathecally into immature rats and its uptake by the lysosomes of the cerebral cortex and the cerebellum was demonstrated. Uptake was assessed in vitro by examining the shift of the lysosomes centrifugal fractions sedimenting at lower speeds than those commonly yielding these granules from control brains. This shift was maximal after 3 daily injections of Triton when arylsulfatase and , the two lysosomal hydrolases studied, exhibited peaks of relative specific activity (RSA) in fractions known to contain myelin fragments and nerve endings rather than in the heavier fraction known to concentrate lysosomes. A significant proportion of the cortical and cerebellar lysosomes failed to take up the detergent even after 3 days of continued administration.The apparent irreversibility of the uptake process was suggested by the finding that the RSA values for the two hydrolases were still highest in the myelin and light nerve ending fractions 4 days after the administration of Triton-WR-1339 had been discontinued. Sedimentation in linear density gradients of sucrose readily separated the populations of Triton-filled and Triton-devoid lysosomes.The results demonstrate the ability of cerebral lysosomes to perform a functional task characteristic of their extracerebral counterparts. It has not been established whether the uptake of Triton-WR-1339 was selective into the lysosomes of neuronal or glial cells or wether it proceeded uniformly into both cell types.