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.
Reinhard
J F
JF
Wellcome Research Laboratories, Research Triangle Park, NC 27709.
Daniels
A J
AJ
Painter
G R
GR
D015655:1-Methyl-4-phenylpyridinium / Q000378:metabolism*; D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured / Q000201:enzymology; D002838:Chromaffin System / Q000378:metabolism*; D003891:Desipramine / Q000378:metabolism; D004058:Diffusion; D004563:Electrochemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015394:Molecular Structure
D007770:L-Lactate Dehydrogenase; D015655:1-Methyl-4-phenylpyridinium; D003891:Desipramine