alpha-Amino-n-butyric acid methyl ester induces concentrative uptake of L-dopa in human Langerhans' cells normally not operative for L-dopa transport.
We recently reported the existence of two kinds of human epidermal Langerhans' cells (LC), one which can take up and accumulate L-dopa and one which cannot. The dopa(+) LC take up L-dopa by carrier-mediated exchange diffusion, that is, the influx of L-dopa and the outflow of an intracellular substance are linked via the same carrier. The nature of the fundamental difference between L-dopa(+) and L-dopa(-) cells has not been clarified. We have now found that alpha-amino-n-butyric acid methyl ester (ABA-OME) penetrates into intracellular compartments, perhaps endosomes or lysosomes, of all LC, where hydrolysis results in the accumulation of the free amino acid (ABA). This accumulation causes a considerable increase in osmotic pressure of the membrane-limited organelle, leading to influx of water and swelling. Co-incubation with L-dopa revealed an influx of L-dopa into LC which normally cannot take up this amino acid. It is suggested that these LC lack the capacity to synthesize and/or store the counterpart which allows L-dopa to enter the dopa(+) LC, but that ABA in the L-dopa(-) LC can function as an equivalent counterpart.
Falck
B
B
Department of Medical Cell Research, University of Lund, Sweden.
Andersson
L
L
Mikulowska
A
A
Ronquist
G
G
D000328:Adult; D000613:Aminobutyrates / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007801:Langerhans Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007980:Levodopa / Q000493:pharmacokinetics*
D000613:Aminobutyrates; C033859:2-aminobutyric acid methyl ester; D007980:Levodopa