Colchicine effects on lysosomal enzyme induction and intracellular degradation in the cultivated macrophage.
The effects of colchicine on lysosomal fusion and lysosomal enzyme induction in the cultivated mouse peritoneal macrophage have been examined. Colchicine (10- minus 6 M), but not lumicolchicine, inhibited lysosomal enzyme induction by both phagocytic and pinocytic stimuli. In addition, the drug significantly retarded pinocytic uptake of [3-H] sucrose and transport of the amino acids [3-H] alpha aminoisobutyric acid and L-[3-H] leucine. In contrast, lumicolchicine had no effect on pinocytosis or amino acid transport. Thus, a role for intact microtubules in lysosomal enzyme induction, pinocytosis, and amino acid uptake in these cells is suggested. That colchicine inhibited lysosomal enzyme induction by phagocytic stimuli under conditions in which pinocytosis contributed little to the enzyme rise indicated that inhibition of pinocytosis was unlikely to account for colchicine effects on lysosomal enzyme induction. Effects of colchicine on degradation of phagocytized and pinocytized substrates were examined to determine if intact microtubules are required for fusion among lysosomes, pinosomes, and phagosomes. Colchicine did not alter the rate of intracellular digestion of radiolabeled bacteria by the cultivated macrophage. Similarly, it had no effect on enzymatic hydrolysis of intracellular [3-H] sucrose resulting from uptake of exogenous invertase. The finding that colchicine had no effect on the functional consequences of fusion of lysosomes with endosomes suggests that intact microtubules are not required for fusion among these constituents of the vacuolar apparatus.
D000135:Acid Phosphatase / Q000096:biosynthesis*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001412:Bacillus subtilis; D002478:Cells, Cultured; D003078:Colchicine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003513:Cycloheximide / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects*; D007930:Leucine / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D010873:Pinocytosis / Q000187:drug effects; D011506:Proteins; D013210:Staphylococcus; D013393:Sucrase / Q000378:metabolism; D013395:Sucrose / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
D000621:Aminoisobutyric Acids; D011506:Proteins; D014316:Tritium; D013395:Sucrose; D003513:Cycloheximide; D000135:Acid Phosphatase; D013393:Sucrase; D007930:Leucine; D003078:Colchicine