Effect of antibiotics on the binding of pargyline to monoamine oxidase in cultured hepatocytes.

ABSTRACT

The laser dye rhodamine 123 has been used to establish that the binding of [3H]pargyline to monoamine oxidase is a more sensitive indicator of mitochondrial perturbation than measurements of protein synthesis, secretion, or degradation. The amount of monoamine oxidase labelled depends on the antibiotic used. The labelling was considerably lower in the presence of gentamycin than in the presence of either chloramphenicol or of penicillin and streptomycin. The accumulation of gentamycin within the cells was the cause of the reduced labelling of monoamine oxidase which was not accompanied by an alteration in the metabolism of pargyline. The gentamycin effect can be prevented by incubating the cells in medium supplemented with methylamine prior to adding the monoamine oxidase inhibitor. Long term culture of cells with gentamycin can result in the cell culture medium becoming dark brown. Under these conditions the monoamine oxidase labelling is increased due to an inhibition of pargyline metabolism. The results indicate that the choice of antibiotic is important in patients being treated with both antibiotics and monoamine oxidase inhibitors.