Journal of Antimicrobial Chemotherapy (1988) 21, 765-772
© 1988 The British Society for Antimicrobial Chemotherapy
research-article |
Uptake of erythromycin by McCoy and HEp2 cells: its dependence on cellular pH gradients
Beecham Pharmaceuticals Research Division Brockham Park, Betchworth, Surrey, RH3 7AJ, UK
Received 28 September 1987; accepted 25 January 1988
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 >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.