Intracellular distribution of gentamicin within the rat kidney cortex: a cell fractionation study.
The present study demonstrates that during the first 1.5-3 min after a single intraperitoneal administration of [3H]gentamicin to rats, most of the radioactivity in the kidney cortex is recovered in the cytosolic and microsomal fractions upon subcellular fractionation. Subsequently, the level of radioactivity recovered in the cytosolic fraction decreases markedly, whereas this level remains relatively unchanged in microsomes and increases somewhat in the nuclear and mitochondrial fractions. A steady state is apparently reached 13 hr after the injection. The high initial concentration of gentamicin in the cytosol may indicate that this substance is taken up to a large extent by diffusion. Such uptake is somewhat surprising, because of the polar nature of gentamicin. The small size of this drug may, however, allow it to diffuse through so-called pores and/or interaction with negatively charged phospholipids may be involved in the uptake of gentamicin. The initial total level of radioactivity recovered in microsomes after in vivo administration of [3H]gentamicin was considerably higher than in the nuclear and mitochondrial-lysosomal fractions. Furthermore, when gentamicin was added directly to kidney homogenate prepared from untreated rats, instead of being administered in vivo, this substance was still recovered in highest amounts in the total microsomal fraction. This observation may indicate that enrichment of gentamicin in the endoplasmic reticulum (or fragments thereof) reflects a special affinity of this drug for these membranes and is probably not the result of a particular in vivo process. There was no difference in the levels of radioactivity recovered in smooth and rough microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)
Nässberger
L
L
Department of Biochemistry, University of Stockholm, Sweden.
Bergstrand
A
A
DePierre
J W
JW
D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D002501:Centrifugation, Zonal; D005839:Gentamicins / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D015388:Organelles / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000378:metabolism; D014316:Tritium
D005839:Gentamicins; D014316:Tritium