Correlation between erythromycin and acid phosphatase in mouse liver.
1. Whole liver homogenates obtained from mice 1h after an intraperitoneal injection of erythromycin lactobionate (343 mg/kg, 1/3 LD 50) were fractionated into nuclear (7000 times g min), mitochondrial (33000 times g min) and lysosomr-rich (250 000 times g min) fractions. 2. The resulting fractions, as well as the final supernatant, were analyzed for erythromycin, acid phosphatase and protein. 3. The highest relative specific activities (per cent total protein) of erythromycin and of acid phosphatase were exhibited by the lysosome-rich fraction. 4. It was of interest, therefore, to examine the effects of erythromycin upon the free activity of acid phosphatase in soluble form and on its in vitro and in vivo release from liver lysosomes. 5. Concentrations of 1.7 - 10-4 M, 3.4 - 10-4 M, 6.8 - 10-4 M and 13. 6 - 10-4 M of erythromycin lactobionate had no significant effect upon the free activity of acid phosphatase in soluble form but retarded the release of this enzyme from the liver lysosome-rich preparation. This effect of erythromycin lactobionate was dose- and time-dependent. 6. Treatment of mice with erythromycin lactobionate (343 mg/kg, 1/3 LD 50) iwtraperitoneally for 7 days significantly decreased the unsedimentable acid phosphatase activity expressed as per cent of total activity in whole liver homogenates. This indicated an in vivo diminished release of acid phosphatase from liver lysosomes by erythromycin. 7. Since erythromycin lactobionate is ionisable it could be possible that erythromycin basis as many other cationic molecules accumulates in lysosomes. 8. The in vitro and in vivo diminished release of acid phosphatase may suggest that erythromycin decreases permeability of lysosomal membrane.
D000135:Acid Phosphatase / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology; D010539:Permeability; D013347:Subcellular Fractions / Q000201:enzymology*
D004917:Erythromycin; D000135:Acid Phosphatase