An interaction of aminoglycoside antibiotics with Ca binding to lipid monolayers and to biomembranes.

Thirteen aminoglycoside antibiotics were investigated with respect to their ability to replace Ca from phosphatidylserine monolayers. The affinities of the glycosides for the Ca-binding sites depended on the pH and the Ca2+ concentration of the aqueous subphase. At a Ca2+ concentration of 1.2 X 10(-5)M and a pH of 7.5 the half maximum concentrations to replace Ca were found to range from 0.4 X 10(-6) (sisomicin) to 6 X 10(-6)M (streptomycin). The interaction between the streptomycins and Ca were of a competitive nature, whereas the aminoglycoside antibiotics with higher affinities displayed unusual steep dose-response curves suggesting positive cooperativity. The aminoglycoside antibiotics were also able to replace Ca from biomembranes (red cell ghosts and isolated sarcolemma of cardiac muscle) in a dose-dependent manner. The high affinity of aminoglycoside antibiotics to a phospholipid is considered to be involved in the toxic side effects of these antibiotics, e.g. nephrotoxicity and impairment of contractile force.