Membrane potential dependence of the kinetics of cationic amino acid transport systems in human placenta.
1. Mediated influx of L-lysine into human placental brush-border membrane vesicles occurs through two systems, one of lower affinity but high capacity, the other of very high affinity but low capacity. These transporters have features characteristic of systems y+ (the classical system) and y+L (recently described in the erythrocyte), respectively. 2. In solutions containing sodium the entry of lysine through the high-affinity system (y+L) is inhibited by the neutral amino acids L-leucine, L-methionine and L-glutamine with comparable high affinity. The removal of sodium reduces the affinity but not the maximal extent of this inhibition. Leucine and methionine, but apparently not glutamine, inhibit lysine entry through system y+ with a much lower affinity. 3. The influx of lysine through system y+ changes markedly in response to alterations of membrane potential. In the presence of an inwardly directed negative diffusion potential created by an inwardly directed thiocyanate (SCN-) gradient, the influx of lysine through this route is accelerated; with an inwardly directed positive potassium diffusion potential, lysine influx through this route is reduced. The influx of lysine through system y+L is much less sensitive to such alterations of potential. 4. Analysis of the kinetic constants characterizing system y+ shows that with a change of potential from zero to negative (approximately -60 mV) the maximum velocity (Vmax) is roughly doubled and the half-saturation constant (Km) halved leading to a 4-fold increase in permeability. For system y+L smaller changes are seen and Km does not change; the resulting increase in y+L permeability is 1.5-fold. 5. These findings are discussed with respect both to the mechanism of membrane transport and placental epithelial function.
Eleno
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Department of Human Anatomy, University of Oxford.
Devés
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Boyd
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CA
D000596:Amino Acids / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D005973:Glutamine / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D008239:Lysine / Q000378:metabolism* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D010920:Placenta / Q000166:cytology / Q000378:metabolism*
D000596:Amino Acids; D002412:Cations; D005973:Glutamine; D008239:Lysine