Influence of membrane surface potential and of net charge on aminoglycoside binding to the organ of Corti of guinea pigs.
Gentamicin binding to homogenates of the organ of Corti of guinea pigs was investigated by altering the magnitude of the membrane surface potential and by testing the potencies of various polyamines and polyamino acids with different numbers of amino groups and different net charge to inhibit or displace bound gentamicin. Diminishing or increasing the ionic strength of the milieu resulted in an increase and a decrease in drug binding, respectively. This observation may be accounted for by the negativity of the membrane surface potential which was enhanced or reduced, when the concentration of cations in the milieu was decreased or increased, respectively. Polyamines and polyamino acids displaced bound gentamicin and inhibited gentamicin binding as a function of the number of amino groups present within the molecule and of their cationic nature. These results point out the importance of considering the surface potential of biological membranes and the net positive charge of the drug in estimating its affinity for the binding site.
Tran Ba Huy
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Inserm U-251, Département de Physiologie, Faculté Xavier-Bichat, Université Paris 7, France.
Deffrennes
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D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D005839:Gentamicins / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009925:Organ of Corti / Q000378:metabolism*; D010455:Peptides / Q000493:pharmacokinetics; D011073:Polyamines / Q000493:pharmacokinetics; D011107:Polylysine / Q000493:pharmacokinetics
D005839:Gentamicins; D010455:Peptides; D011073:Polyamines; D011107:Polylysine; C017645:polyaspartate; C045164:polyasparagine