EFFECTS OF 3 AMINOGLYCOSIDE ANTIBIOTICS (KANAMYCIN, GENTAMICIN AND FRADIOMYCIN) ON THE THROMBIN-INDUCED AGGREGATION AND INTRACELLULAR Ca²⁺ MOBILIZATION OF HUMAN PLATELETS

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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.
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⁺.
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.