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PMID: 1930152 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Inhibition of neural phospholipase D activity by aminoglycoside antibiotics.

The Biochemical journal ·Vol. 279 ( Pt 1) ·1991-10-01 ·Pages 319-21

Liscovitch M, Chalifa V, Danin M, Eli Y

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.

MeSH Terms
Aminoglycosides Animals Anti-Bacterial Agents/pharmacology Brain/cytology,drug effects,enzymology Cells, Cultured Guanosine 5'-O-(3-Thiotriphosphate)/metabolism Phospholipase D/antagonists & inhibitors Rats
Chemicals
Aminoglycosides Anti-Bacterial Agents Guanosine 5'-O-(3-Thiotriphosphate) Phospholipase D
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liscovitch M
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Chalifa V
Danin M
Eli Y
References (14)
14 references, click to expand
  1. Gonadotropin-releasing hormone activates phospholipase D in ovarian granulosa cells. Possible role in signal transduction.
    J Biol Chem. 1989 Jul 15;264(20):11762-7 PMID: 2663840
  2. Signaling through phosphatidylcholine breakdown.
    J Biol Chem. 1990 Jan 5;265(1):1-4 PMID: 2104616
  3. The regulation and cellular functions of phosphatidylcholine hydrolysis.
    Biochem J. 1990 Jul 15;269(2):281-91 PMID: 2201284
  4. A neutral phospholipase D activity from rat brain synaptic plasma membranes. Identification and partial characterization.
    J Biol Chem. 1990 Oct 15;265(29):17512-9 PMID: 2211645
  5. 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):2885-91 PMID: 1702786
  6. Signal-dependent activation of phosphatidylcholine hydrolysis: role of phospholipase D.
    Biochem Soc Trans. 1991 Apr;19(2):402-7 PMID: 1889622
  7. Receptor regulation of choline phospholipid hydrolysis. A novel source of diacylglycerol and phosphatidic acid.
    Biochem Pharmacol. 1989 May 15;38(10):1543-9 PMID: 2543416
  8. Aminoglycoside inhibition of a renal phosphatidylinositol phospholipase C.
    J Pharmacol Exp Ther. 1982 Feb;220(2):287-92 PMID: 6276533
  9. Identification of the aminoglycoside binding site in rat renal brush border membranes.
    J Pharmacol Exp Ther. 1982 Aug;222(2):350-8 PMID: 7097555
  10. Characterization of aminoglycoside-lipid interactions and development of a refined model for ototoxicity testing.
    Biochem Pharmacol. 1984 Oct 15;33(20):3257-62 PMID: 6487373
  11. Effects of aminoglycosides on proximal tubule brush border membrane phosphatidylinositol-specific phospholipase C.
    J Pharmacol Exp Ther. 1984 Oct;231(1):48-55 PMID: 6092605
  12. 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):815-9 PMID: 3663101
  13. 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):1450-6 PMID: 2912965
  14. Purification of Streptomyces chromofuscus phospholipase D by hydrophobic affinity chromatography on palmitoyl cellulose.
    J Biochem. 1979 Jan;85(1):79-95 PMID: 762053
Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
Published
1991-10-01
Pages
319-21
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1151584
Subset
IM
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