Ontogenic and longitudinal activity of Na(+)-nucleoside transporters in the human intestine.
The objectives of our study were to identify the types of nucleoside transporters present in the human fetal small intestine and to characterize their developmental activity, longitudinal distribution, and transport kinetics compared with those present in the adult intestine. Nucleoside uptake by intestinal brush-border membrane vesicles was measured by an inhibitor-stop rapid filtration technique. Only the purine-specific (N1; hCNT2) and the pyrimidine-specific (N2; hCNT1) Na(+)-dependent nucleoside transporters were found to be present on the brush-border membranes of the enterocytes along the entire length of the fetal and adult small intestines. The activity of these transporters was higher in the proximal than in the distal small intestine. Both the N1 and N2 transporters found in the fetal intestine shared similar kinetic properties (Michaelis-Menten constant and Na(+)-nucleoside stoichiometry) to those in the adult intestine. During the period of rapid morphogenesis (11-15 wk gestation), no temporal differences were apparent in the activity of the N1 and N2 transporters in the fetal small intestine. These findings have implications for the absorption of drugs from the amniotic fluid by the fetus after maternal drug administration of nucleoside drugs such as the antivirals zidovudine and didanosine.
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Department of Pharmaceutics, University of Washington, Seattle, Washington 98195, USA.
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D000328:Adult; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D003562:Cytidine / Q000493:pharmacokinetics; D022162:Cytoplasmic Vesicles / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D005260:Female; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006151:Guanosine / Q000493:pharmacokinetics; D006801:Humans; D007288:Inosine / Q000493:pharmacokinetics; D007421:Intestine, Small / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins; D008871:Microvilli / Q000378:metabolism; D009928:Organ Specificity; D020033:Protein Isoforms; D012964:Sodium / Q000378:metabolism; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014529:Uridine / Q000493:pharmacokinetics
D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; C065171:cif nucleoside transporter; D006151:Guanosine; D013868:Thioinosine; D007288:Inosine; D003562:Cytidine; D012964:Sodium; C001789:4-nitrobenzylthioinosine; D014529:Uridine