Transport of phenylethylamine at intestinal epithelial (Caco-2) cells: mechanism and substrate specificity.
This study was performed to characterize the intestinal transport of beta-phenylethylamine (PEA). Uptake of [(14)C]PEA into Caco-2 cells was Na(+)-independent but strongly stimulated by an outside directed H(+) gradient. At extracellular pH 7.5, the concentration-dependent uptake of PEA was saturable with kinetic parameters of 2.6mM (K(t)) and 96.2nmol/min per mg of protein (V(max)). Several biogenic amines such as harmaline and N-methylphenylethylamine as well as cationic drugs such as phenelzine, tranylcypromine, d,l-amphetamine, methadone, chlorphenamine, diphenhydramine and promethazine strongly inhibited the [(14)C]PEA uptake with K(i) values around 1mM. Tetraethylammonium, N-methyl-4-phenylpyridinium and choline had no effect. We also studied the bidirectional transepithelial transport of [(14)C]PEA at cell monolayers cultured on permeable filters. Net transepithelial flux of [(14)C]PEA from apical-to-basolateral side exceeded basolateral-to-apical flux 5-fold. We conclude that PEA is transported into Caco-2 cells by a highly active, saturable, H(+)-dependent (antiport) process. The transport characteristics do not correspond to those of the known carriers for organic cations of the SLC22, SLC44, SLC47 and other families.
Fischer
Wiebke
W
Biozentrum of the Martin-Luther-University Halle-Wittenberg, Halle, Germany.
Neubert
Reinhard H H
RH
Brandsch
Matthias
M
D001693:Biological Transport, Active / Q000187:drug effects*; D018938:Caco-2 Cells; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007700:Kinetics; D010627:Phenethylamines / Q000493:pharmacokinetics*; D011869:Radioligand Assay / Q000379:methods; D013379:Substrate Specificity
D010627:Phenethylamines; C029261:phenethylamine