Localization of d-tubocurarine in rat liver lysosomes

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Abstract
In the rat d-tubocurarine is taken up by the liver and excreted in bile. A fraction of the drug is taken up very rapidly by lysosomes. This lysosomal localization of the drug was demonstrated by purification of Triton WR 1339 loaded lysosomes (‘tritosomes’) on a sucrose density gradient by flotation; 3H-labeled d-tubocurarine was accumulated in the same fractions as acid phosphatase activity. Lysosome-bound d-tubocurarine is not available for biliary excretion and remains in the lysosomes even when the cytosolic concentration decreases to very low levels. The biliary excretion rate was linearly related to the amount of d-tubocurarine present in the cytosol. Lysosomal uptake of d-tubocurarine was decreased or prevented by the basic drug quinacrine in vivo. The lysosomal storage of d-tubocurarine is discussed in relation to its relevance for the clinical use of this and related drugs.