Transport mechanisms of the large neutral amino acid L-phenylalanine in the human intestinal epithelial caco-2 cell line.
The transepithelial transport and the intracellular accumulation of the large neutral amino acid L-phenylalanine (L-Phe) were studied in monolayers of Caco-2 cells, cultivated in a bicameral insert system, to characterize the mechanisms involved in the absorption of this essential amino acid by the human intestinal mucosa. In our model, L-Phe was transported selectively in the apical (AP)-to-basolateral (BL) direction. AP-to-BL transport of L-Phe was temperature dependent and Na(+) independent, increased in the absence of protein synthesis and showed competition with large neutral and cationic amino acids. By contrast, transport in the BL-to-AP direction mainly resulted from passive movement (probably paracellular passage and transcellular diffusion). L-Phe accumulation into Caco-2 cells was higher from the BL pole than from the AP pole and characterized by the incorporation of most of the accumulated molecules into newly synthesized proteins. In addition, L-Phe accumulation was Na(+) dependent from both poles, whereas only accumulation from the AP pole was sensitive to inhibition by both large neutral and cationic amino acids. These results suggest that the processes involved in AP-to-BL transport and AP accumulation of this amino acid are very different from those involved in BL-to-AP transport and BL accumulation.
Berger
V
V
Laboratoire de Biochimie Cellulaire, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
Larondelle
Y
Y
Trouet
A
A
Schneider
Y J
YJ
D001692:Biological Transport; D001711:Biotransformation; D018938:Caco-2 Cells; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008567:Membranes, Artificial; D010649:Phenylalanine / Q000493:pharmacokinetics*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D008567:Membranes, Artificial; D011500:Protein Synthesis Inhibitors; D010649:Phenylalanine; D003513:Cycloheximide