CARRIER-INDEPENDENT ENTRY OF 1-METHYL-4-PHENYLPYRIDINIUM (MPP+) INTO ADRENAL CHROMAFFIN CELLS AS A CONSEQUENCE OF CHARGE DELOCALIZATION

The administration of 1-methyl-4-phenylpyridinium (MPP+) to cultures of adrenal medullary chromaffin cells resulted in time and concentration-dependent increases in the cellular content of MPP+. Co-incubation of cells with MPP+, in the presence of desmethylimipramine (DMI), reduced but did not prevent the accumulation of the pyridinium in these cells. Similarly, DMI and MPP+ co-administration reduced but did not prevent the neurotoxicant-induced release of a cytosolic marker, lactate dehydrogenase, into the media. Molecular orbital calculations reveal that the positive charge of MPP+ is highly delocalized throughout the pyridinium ring and consequently MPP+ may be able to diffuse down concentration or charge gradients. Thus, these data provide a basis for the entry of MPP+ into cells and subcellular organelles that lack a catecholamine transporter, e.g. mitochondria. © 1990.