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. Copyright (c) 2009 Elsevier B.V. All rights reserved.