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Uptake of erythromycin by McCoy and HEp2 cells: its dependence on cellular pH gradients.

The accumulation of erythromycin, a weak lipophilic base, was studied in two mammalian cell lines. Uptake was similar in both cell types, being highly pH dependent and not saturated even at external concentrations of 1000 mg/l. At pH 6.7 the ratio of cellular:extracellular erythromycin concentrations (C/E) was only 2.0, whereas at pH 7.5 it was as high as 7.0. Carbonylcyanide-m-chlorophenyl hydrazone, an uncoupler of oxidative phosphorylation which was used to collapse cellular pH gradients, caused a 50% reduction in C/E ratio within five minutes when the external pH was greater than 6.9 but had no effect at or below pH 6.7. These results suggest that ion-trapping plays a major role in the accumulation of erythromycin by these cells.