EFFECTS OF 3 AMINOGLYCOSIDE ANTIBIOTICS (KANAMYCIN, GENTAMICIN AND FRADIOMYCIN) ON THE THROMBIN-INDUCED AGGREGATION AND INTRACELLULAR Ca<SUP>2+</SUP> MOBILIZATION OF HUMAN PLATELETS
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- TANIHATA SACHIKO
- Department of Pharmacology, Toho University School of Medicine
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- UCHIYAMA TOSHIMITSU
- Department of Pharmacology, Toho University School of Medicine
抄録
This study was aimed at determining whether the thrombin (TRB)-induced aggregation and intracellular free Ca2+ ([Ca2+]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 [Ca2+]i mobilization are pH-dependent.<BR>TRB (0.1U/ml) induced aggregation in the presence of 1mm 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 [Ca2+]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 [Ca2+]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+.<BR>These results suggest that the reducing potency of the 3 AGs in the TRB-induced aggregation and Ca2+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.
収録刊行物
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- The Japanese Journal of Antibiotics
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The Japanese Journal of Antibiotics 46 (3), 242-250, 1993
公益財団法人 日本感染症医薬品協会