Binding of aminocyclitol antibiotics to kidney and intestinal brush border membranes.
Binding of aminocyclitol antibiotics to intestinal and kidney brush border membranes has been studied in vitro by means of vesicular preparations. The binding is rapid, reversible, specific, saturable and has a high affinity. To both tissues, gentamicin and sisomicin bind to a single binding site or receptor. These antibiotics demonstrate increased binding under conditions of increasing pH. Membrane binding disappears when the vesicle proteins are denatured with TCA. A significant reduction in aminocyclitol binding after treatment of vesicles with papain indicates that a portion of the binding receptor protein is exposed to the outer surface of the brush border membrane. The accumulated evidence suggests that the nature of the binding mechanism is not a simple electrostatic interaction between the antibiotic's charged amino groups and the polyanions of the membrane. Alternatively, a specific membrane structure is required for binding whose characteristics reflect a drug-receptor interaction. Receptor binding is characterized as being saturable, reversible, and specific; all of which have been demonstrated for aminocyclitols and brush border membranes.
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism*; D005839:Gentamicins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007477:Ions; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism*; D010206:Papain / Q000494:pharmacology; D011817:Rabbits; D012853:Sisomicin / Q000378:metabolism*
D005839:Gentamicins; D007477:Ions; D010206:Papain; D002118:Calcium; D012853:Sisomicin