Open AccessNeomycin inhibits platelet functions and inositol phospholipid metabolism upon stimulation with thrombin, but not with ionomycin or 12‐ O ‐tetradecanoyl‐phorbol 13‐acetate
Author(s) -
TYSNES OleBjØrn,
STEEN Vidar M.,
HOLMSEN Holm
Publication year - 1988
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1988.tb14365.x-i2
Subject(s) - ionomycin , stimulation , inositol , phorbol , chemistry , thrombin generation , neomycin , thrombin , phospholipid , platelet , microbiology and biotechnology , endocrinology , pharmacology , medicine , biochemistry , signal transduction , biology , protein kinase c , receptor , membrane , antibiotics
Gel‐filtered human platelets that had been pre‐labelled with [ 32 P]P i were stimulated with thrombin, ionomycin or the phorbol ester 12‐ O ‐tetradecanoyl‐phorbol 13‐acetate (TPA). The effect of the hexacationic aminoglycoside antibiotic, neomycin, on platelet physiological responses, such as aggregation and secretion, as well as changes in phosphoinositide metabolism was studied. Neomycin strongly inhibited thrombin‐induced aggregation and secretion whereas the antibiotic had no effect on ionomycin‐ or TPA‐induced platelet functions. The thrombin‐induced enhancement of inositol phospholipid metabolism was strongly inhibited by the presence of neomycin whereas the TPA‐ or ionomycin‐induced increase in inositol [ 32 P]polyphospholipids remained unaffected. The inhibitory effect of some other aminoglycoside antibiotics was compared to that of neomycin and the data demonstrate that the inhibition of platelet secretion and phosphatidic acid production was dependent on the cationic charge of the antibiotic. It is suggested that neomycin inhibits signal transduction in platelets at a level prior to the inositol‐phospholipid‐specific phosphodiesterase.