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. 1991 Oct 1;279(Pt 1):319–321. doi: 10.1042/bj2790319

Inhibition of neural phospholipase D activity by aminoglycoside antibiotics.

M Liscovitch 1, V Chalifa 1, M Danin 1, Y Eli 1
PMCID: PMC1151584  PMID: 1930152

Abstract

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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aridor M., Sagi-Eisenberg R. Neomycin is a potent secretagogue of mast cells that directly activates a GTP-binding protein involved in exocytosis. J Cell Biol. 1990 Dec;111(6 Pt 2):2885–2891. doi: 10.1083/jcb.111.6.2885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Billah M. M., Anthes J. C. The regulation and cellular functions of phosphatidylcholine hydrolysis. Biochem J. 1990 Jul 15;269(2):281–291. doi: 10.1042/bj2690281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chalifa V., Möhn H., Liscovitch M. A neutral phospholipase D activity from rat brain synaptic plasma membranes. Identification and partial characterization. J Biol Chem. 1990 Oct 15;265(29):17512–17519. [PubMed] [Google Scholar]
  4. Exton J. H. Signaling through phosphatidylcholine breakdown. J Biol Chem. 1990 Jan 5;265(1):1–4. [PubMed] [Google Scholar]
  5. Imamura S., Horiuti Y. Purification of Streptomyces chromofuscus phospholipase D by hydrophobic affinity chromatography on palmitoyl cellulose. J Biochem. 1979 Jan;85(1):79–95. doi: 10.1093/oxfordjournals.jbchem.a132334. [DOI] [PubMed] [Google Scholar]
  6. Lipsky J. J., Lietman P. S. Aminoglycoside inhibition of a renal phosphatidylinositol phospholipase C. J Pharmacol Exp Ther. 1982 Feb;220(2):287–292. [PubMed] [Google Scholar]
  7. Liscovitch M., Amsterdam A. Gonadotropin-releasing hormone activates phospholipase D in ovarian granulosa cells. Possible role in signal transduction. J Biol Chem. 1989 Jul 15;264(20):11762–11767. [PubMed] [Google Scholar]
  8. Liscovitch M. Phosphatidylethanol biosynthesis in ethanol-exposed NG108-15 neuroblastoma X glioma hybrid cells. Evidence for activation of a phospholipase D phosphatidyl transferase activity by protein kinase C. J Biol Chem. 1989 Jan 25;264(3):1450–1456. [PubMed] [Google Scholar]
  9. Liscovitch M. Signal-dependent activation of phosphatidylcholine hydrolysis: role of phospholipase D. Biochem Soc Trans. 1991 Apr;19(2):402–407. doi: 10.1042/bst0190402. [DOI] [PubMed] [Google Scholar]
  10. Löffelholz K. Receptor regulation of choline phospholipid hydrolysis. A novel source of diacylglycerol and phosphatidic acid. Biochem Pharmacol. 1989 May 15;38(10):1543–1549. doi: 10.1016/0006-2952(89)90299-2. [DOI] [PubMed] [Google Scholar]
  11. Polascik T., Godfrey P. P., Watson S. P. Neomycin cannot be used as a selective inhibitor of inositol phospholipid hydrolysis in intact or semi-permeabilized human platelets. Aminoglycosides activate semi-permeabilized platelets. Biochem J. 1987 May 1;243(3):815–819. doi: 10.1042/bj2430815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sastrasinh M., Knauss T. C., Weinberg J. M., Humes H. D. Identification of the aminoglycoside binding site in rat renal brush border membranes. J Pharmacol Exp Ther. 1982 Aug;222(2):350–358. [PubMed] [Google Scholar]
  13. Schwertz D. W., Kreisberg J. I., Venkatachalam M. A. Effects of aminoglycosides on proximal tubule brush border membrane phosphatidylinositol-specific phospholipase C. J Pharmacol Exp Ther. 1984 Oct;231(1):48–55. [PubMed] [Google Scholar]
  14. Wang B. M., Weiner N. D., Takada A., Schacht J. Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing. Biochem Pharmacol. 1984 Oct 15;33(20):3257–3262. doi: 10.1016/0006-2952(84)90087-x. [DOI] [PubMed] [Google Scholar]

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