Inhibition of neural phospholipase D activity by aminoglycoside antibiotics.
The effects of aminoglycoside antibiotics on phospholipase D (PLD) activity were investigated in permeabilized NG108-15 cells and in isolated rat brain membranes. Neomycin inhibited guanosine 5'-[gamma-thio]triphosphate-stimulated PLD activity in digitonin-permeabilized NG108-15 cells in a concentration-dependent manner (50% inhibition at 100 microM). Neomycin similarly inhibited PLD activity present in rat brain membranes and assayed in vitro with [3H]phosphatidylcholine as substrate (50% inhibition at 65 microM). Other aminoglycosides tested (kanamycin, geneticin and streptomycin) were nearly equipotent inhibitors of rat brain PLD. These results indicate that aminoglycoside antibiotics inhibit phosphatidylcholine-PLD activity with comparable and sometimes greater potency than their well known inhibition of phosphoinositide-phospholipase C. The possibility that PLD inhibition could mediate some of the toxic side effects of aminoglycosides is suggested.
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
M
M
Liscovitch
V
V
Chalifa
M
M
Danin
Y
Y
Eli
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors*; D051381:Rats
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010739:Phospholipase D