Phospholipids aminoglycosides

Tab. 4.39 Binding of aminoglycosides to phospholipids, energy of aminoglycoside-phospholipid interaction, and inhibition of phospholipase A, activity. (Reprinted from Tab. 1 of ref. 138 with permission from Elsevier Science)...

Aminoglycoside binding to membrane acidic phospholipids Changes in content and metabolism of membrane phospholipids Displacement of calcium bound to phospholipids Formation of myeloid bodies... 

After the initial binding to the anionic phospholipids of the PTC, the aminoglycoside molecule is quickly transferred to the transmembrane protein megalin and endocytosed [42, 43, 48-50, 52-59, 66-68, 72, 73]. Aminoglycosides enter the PTC on either the apical or basolateral plasma membrane via receptor-mediated endocytosis. and are ultimately sequestered in the same endosomal compartment [68]. In an experiment with LLC-PKl cells. Ford et al. demonstrated that aminoglycosides were internalized equally across the apical and basolateral membranes by receptor-mediated endocytosis. This was followed by colocalization within the lysosomal compartment and similar magnitudes of cellular dysfunction [68]. 

Metabolic acidosis and electrolyte disturbances. Acidic environments increase the ionization of aminoglycosides and positive cations compete with the aminoglycosides for binding sites. Consequently, metabolic acidosis and electrolyte imbalances such as hypokalemia and hyponatremia increase the binding of aminoglycosides to the phospholipid receptors on the renal tubular cells, increasing intracellular accumulation. 

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