Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (7): Effect of latamoxef on binding of tobramycin to brush border membranes isolated from rat kidney cortex.
We investigated the effect of latamoxef (LMOX) on the binding of tobramycin (TOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation. The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 micrograms protein) significantly inhibited the binding of TOB to BBMs. The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37 degrees C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs. Although [14C]-labeled LMOX was taken up by BBMs temperature- and time-dependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs. Additionally, the binding of TOB to the LMOX-treated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37 degrees C was similar to that of TOB to the non-treated BBMs. These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB.
Kojima
R
R
Department of Pharmacology, Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Ito
M
M
Suzuki
Y
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008854:Microscopy, Electron; D008871:Microvilli / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009070:Moxalactam / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014031:Tobramycin / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D009070:Moxalactam; D014031:Tobramycin