Characteristics of histidine uptake by human placental microvillous membrane vesicles.
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 degrees 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 L-histidine 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 inhibit L-histidine uptake. Conversely, L-histidine noncompetitively inhibited sodium-dependent uptake of 2-(methylamino)isobutyric acid and L-cysteine. 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Karl
P I
PI
Department of Pediatrics and Research, North Shore University Hospital, Manhasset, New York.
Tkaczevski
H
H
Fisher
S E
SE
D000621:Aminoisobutyric Acids / Q000493:pharmacokinetics; D000838:Anions / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D002412:Cations / Q000378:metabolism; D003545:Cysteine / Q000493:pharmacokinetics; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D005942:Gluconates / Q000378:metabolism; D005973:Glutamine / Q000493:pharmacokinetics; D006639:Histidine / Q000493:pharmacokinetics*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008871:Microvilli / Q000378:metabolism; D009994:Osmolar Concentration; D010649:Phenylalanine / Q000493:pharmacokinetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012964:Sodium / Q000378:metabolism; D013696:Temperature
D000621:Aminoisobutyric Acids; D000838:Anions; D002412:Cations; D005942:Gluconates; D005973:Glutamine; C017911:2-(methylamino)isobutyric acid; D010649:Phenylalanine; D006639:Histidine; D012964:Sodium; D003545:Cysteine; D005033:Ethylmaleimide