Abstract
ABSTRACT: L-histidine is an essential amino acid. Its fetal-to-maternal blood concentration ratio is high, suggesting active placental transport. In this study, human placental microvillous membrane vesicles were used to characterize L-histidine transport, heretofore not evaluated in human tissue. L-Histidine uptake by microvillous membrane vesicles was stimulated by an inward sodium gradient, leading to an “overshoot,” followed by apparent equilibration. Linear uptake at 22° C was limited to the 1st min. The initial sodium-dependent uptake rate was proportional to the sodium concentration in the medium. The sodium-dependent uptake was markedly diminished or lost when potassium, cesium, or choline was substituted for sodium but not lithium. Replacement of chloride with sulfate or gluconate had little effect. Sodium-stimulated Lhistidine uptake was further stimulated by an outward potassium gradient (inside-negative) in the presence of valinomycin. Sodium-dependent uptake kinetic constants for L-histidine were: Km=0.44 ± 0.18 mM: Vmax = 536 ± 94 nmol/mg/30 s (mean ± SD). 2-(methylamino) isobutyric acid did not inhibite L-histidine uptake. Conversely, L-histidine noncompetitively inhibited sodium-dependent uptake of 2-(methylamino)isobutyric acid and Lcysteine. L-glutamine competitively inhibited sodium-dependent L-histidine uptake. L-histidine uptake was stimulated by preloading the vesicles with either L-histidine or L-glutamine (transstimulation). L-histidine uptake was not sensitive to N-ethylmaleimide treatment but was strongly inhibited by low pH. These findings suggest that L-histidine is transported in the human placenta by a specific sodium-dependent system similar to the “N” system described in rodent hepatocytes. Furthermore, the ready availability of placental tissue may make it a useful resource for studies of human epithelial transport biology.
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Karl, P., Tkaczevski, H. & Fisher, S. Characteristics of Histidine Uptake by Human Placental Microvillous Membrane Vesicles. Pediatr Res 25, 19–26 (1989). https://doi.org/10.1203/00006450-198901000-00005
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DOI: https://doi.org/10.1203/00006450-198901000-00005
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