Neomycin inhibits inositol phosphate formation in human platelets stimulated by thrombin but not other agonists

Abstract

Neomycin (0.1–1 mM) added to human platelet-rich plasma or washed platelets prelabeled with [ 3H]inositol inhibits aggregation, ATP secretion (ID 50 0.2 mM) and formation of [ 3H]inositol mono-, bis- and trisphosphate (ID 50 0.6–0.8 mM) in response to thrombin (0.25 U ml ). The production of inositol phosphates in response to other platelet agonists (vasopressin, platelet activating factor, prostaglandin endoperoxide analogs and collagen) is not inhibited by neomycin, even at a concentration of 2 mM. At this concentration neomycin reduces the secretion of ATP stimulated by these agents (by up to 50%). The results indicate that neomycin has multiple effects on platelets that are unrelated to a specific inhibition of inositol phospholipid degradation by phospholipase C. Low concentrations (0.1–1 mM) of neomycin might selectively inhibit the interaction of thrombin with the platelet surface, and high concentrations (> 2 mM) might unspecifically reduce platelet secretion in response to various platelet agonists.