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

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• 作者：Wiebke Fischer ; Reinhard H.H. Neubert ; Matthias Br ; sch
• 关键词：Biogenic amines ; Caco-2 cells ; Drug delivery ; Intestinal epithelium ; Membrane transport ; Phenylethylamine (PEA)
• 刊名：European Journal of Pharmaceutics and Biopharmaceutics
• 出版年：2010
• 出版时间：February 2010
• 年：2010
• 卷：74
• 期：2
• 页码：281-289
• 全文大小：1234 K

文摘

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 (K_t) and 96.2 nmol/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 [¹⁴C]PEA uptake with K_i 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.