Transport of phenylethylamine at intestinal epithelial (Caco-2) cells: Mechanism and substrate specificity

This study was performed to characterize the intestinal transport of β-phenylethylamine (PEA). Uptake of [14C]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 2.6 mM (Kt) and 96.2 nmol/min per mg of protein (Vmax). 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 [14C]PEA uptake with Ki values around 1 mM. Tetraethylammonium, N-methyl-4-phenylpyridinium and choline had no effect. We also studied the bidirectional transepithelial transport of [14C]PEA at cell monolayers cultured on permeable filters. Net transepithelial flux of [14C]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.