Neomycin sulfate is an aminoglycoside antibiotic used for preventing or treating bacterial infections.
Neomycin inhibits thrombin-stimulated release of inositol 1,4,5-trisphosphate (IP3), by selectively binding PIP2, but does not inhibit 32P incorporation into PI or initiation of DNA synthesis[1]. Neomycin (10 μM-1 mM) induces considerable release of [3H]arachidonic acid from phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine in saponin-permeabilized human platelets prelabeled with [3H]arachidonic acid. Moreover, neomycin enhances arachidonic acid release induced by thrombin. Addition of neomycin (100 μM) to 45Ca2+-preloaded platelets elicits 45Ca2+ mobilizatioin from intracellular stores[2]. Neomycin (0-10 mM) inhibits guanosine 5'-[gamma-thio]triphosphate-stimulated PLD activity in digitonin-permeabilized NG108-15 cells in a concentration-dependent manner (50% inhibition at 100 μM). Neomycin similarly inhibits PLD activity present in rat brain membranes and assayed in vitro with [3H]phosphatidylcholine as substrate (50% inhibition at 65 μM)[3]. Neomycin (5 mM) causes reversible reductions in the level of intracellular Ca2+, but PtdIns(4,5)P2 is not required for the channel activity[4].
References:
[1]. Carney, D.H., et al. Phosphoinositides in mitogenesis: neomycin inhibits thrombin-stimulated phosphoinositide turnover and initiation of cell proliferation. Cell, 1985. 42(2): p. 479-88.
[2]. Nakashima, S., et al. Neomycin is a potent agent for arachidonic acid release in human platelets. Biochem Biophys Res Commun, 1987. 146(2): p. 820-6.
[3]. Liscovitch, M., et al., Inhibition of neural phospholipase D activity by aminoglycoside antibiotics. Biochem J, 1991. 279 ( Pt 1): p. 319-21.
[4]. Huang K, et al. CRAC channel is inhibited by neomycin in a Ptdlns(4,5)P2-independent manner. Cell Biochem Funct. 2015 Mar;33(2):97-100.