Neomycin inhibits inositol phosphate formation in human platelets stimulated by thrombin but not other agonists.
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 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 (greater than 2 mM) might unspecifically reduce platelet secretion in response to various platelet agonists.
D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis*; D009355:Neomycin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D013403:Sugar Phosphates / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000032:analysis
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D000255:Adenosine Triphosphate; D010738:Type C Phospholipases; D013917:Thrombin; D009355:Neomycin