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 (ID50 0.2 mM) and formation of [3H]inositol mono-, bis- and trisphosphate (ID50 0.6–0.8 mM) in response to thrombin (0.25 Uml). 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