Effects of 3 aminoglycoside antibiotics (kanamycin, gentamicin and fradiomycin) on the thrombin-induced aggregation and intracellular Ca2+ mobilization of human platelets.
This study was aimed at determining whether the thrombin (TRB)-induced aggregation and intracellular free Ca2+ ([Ca(2+)]i) mobilization of fura-2-loaded human platelets would be affected by aminoglycoside antibiotics (AGs), i.e., kanamycin (KM), gentamicin (GM) and fradiomycin (FRM) with 4, 5 and 6 amino groups in their molecules, respectively. We used pH-adjusted solution of AGs, since the TRB-induced aggregation and [Ca(2+)]i mobilization are pH-dependent. TRB (0.1 U/ml) induced aggregation in the presence of 1 mM external Ca2+ but did not in the absence of external Ca2+. The 3 AGs reduced the TRB-induced aggregation and the antiaggregating potencies were in the order FRM = GM > KM. TRB-induced [Ca(2+)]i elevation in the presence of external Ca2+ was 3 times higher than in the absence of external Ca2+ and the 3 AGs concentration-dependently reduced the TRB-induced [Ca(2+)]i elevation in the absence of external Ca2+ as well as in its presence, and the potency order was FRM > GM > KM. The IC50 of GM or KM was higher in the absence of external Ca2+ than in its presence, while the IC50 of FRM was scarcely affected by the deprivation of external Ca2+. These results suggest that the reducing potency of the 3 AGs in the TRB-induced aggregation and [Ca(2+)]i mobilization of human platelets is based on the number of amino groups. Furthermore, it is suggested that GM and KM predominantly reduce the Ca2+ influx rather than the intracellular Ca2+ release but FRM is equieffective in decreasing both of them.
Department of Pharmacology, Toho University School of Medicine.
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Tanihata
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Uchiyama
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood* / Q000502:physiology; D002478:Cells, Cultured; D005839:Gentamicins / Q000494:pharmacology; D006801:Humans; D007612:Kanamycin / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D010975:Platelet Aggregation Inhibitors; D007612:Kanamycin; D013917:Thrombin; D009355:Neomycin; D002118:Calcium