Inhibition of the L-dopa transport system in human epidermal Langerhans cells by omeprazole and its analogues.
L-3,4-dihydroxyphenylalanine (L-dopa) transport into human Langerhans cells (LC) occurs by a saturable mediation. This plasma membrane agency is, due to its characteristics, distinguishable from systems transporting other neutral, cationic and anionic amino acids into other cells and serves to catalyze the flow of L-dopa, only, into LC. The uphill operation of this L-dopa transport system is believed to occur by down-gradient countermigration of H(+). Due to the uniqueness of the L-dopa transport system, the widely used analogue inhibition approach was not applicable. Instead we studied omeprazole and its analogues in our search for suitable inhibitory candidates. Omeprazole and most of its analogues were indeed inhibitory in the concentration range 1-100 micromol/L. Conspicuously, the compounds with strongest polarity were least inhibitory. The inhibitory pattern displayed by omeprazole and the other analogues on L-dopa uptake in LC corresponded to some extent to what has been observed previously for purified H(+),K(+)-ATPase from tubulovesicles of the stomach. No effects of the inhibitors were registered on energy charge and lactate production of epidermal biopsies, nor were any gross alterations of ultrastructure of LC noticed.
Bendsoe
N
N
Department of Medical Microbiology, Lund University, Lund, Sweden.
Ronquist
G
G
D000251:Adenosine Triphosphatases / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000078404:Epidermal Cells; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D007801:Langerhans Cells / Q000378:metabolism*; D007980:Levodopa / Q000378:metabolism*; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism
D004791:Enzyme Inhibitors; D019344:Lactic Acid; D007980:Levodopa; D006859:Hydrogen; D000251:Adenosine Triphosphatases; D009853:Omeprazole; D011188:Potassium