H+/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat

Catriona M. H. Anderson, Danielle S. Grenade, Michael Boll, Martin Foltz, Katherine A. Wake, David J. Kennedy, Lars K. Munck, Seiji Miyauchi, Peter M. Taylor, Frederick Charles Campbell, Bjarne G. Munck, Hannelore Daniel, Vadivel Ganapathy, David T. Thwaites

    Research output: Contribution to journalArticlepeer-review

    118 Citations (Scopus)


    Background & Aims: Amino acid (and related drug) absorption across the human small intestinal wall is an essential intestinal function. Despite the revelation of a number of mammalian genomes, the molecular identity of the classic Na+-dependent imino acid transporter (identified functionally in the 1960s) remains elusive. The aims of this study were to determine whether the recently isolated complementary DNA hPAT1 (human proton-coupled amino acid transporter 1), or solute carrier SLC36A1, represents the imino acid carrier; the Na+-dependent imino acid transport function measured at the brush-border membrane of intact intestinal epithelia results from a close functional relationship between human proton-coupled amino acid transporter-1. and Na+/H+ exchanger 3 (NHE3). Methods: PAT1 function was measured in isolation (Xenopus laevis oocytes) and in intact epithelia (Caco-2 cell monolayers and rat small intestine) by measurement of amino acid and/or H+ influx. Tissue and membrane expression of PAT1 were determined by reverse-transcription polymerase chain reaction and immunohistochemistry. Results: PAT1-specific immunofluorescence was localized exclusively to the luminal membrane of Caco-2 cells and human and rat small intestine. The substrate specificity of hPAT1 is identical to that of the imino acid carrier. In intact epithelia, PAT1-mediated amino acid influx is reduced under conditions in which NHE3 is inactive. Conclusions: The identification in intact epithelia of a cooperative functional relationship between PAT1 (H+/amino acid symport) and NHE3 (Na+/H+ exchange) explains the apparent Na+ dependence of the imino acid carrier in studies with mammalian intestine. hPAT1 is the high-capacity imino acid carrier localized at the small intestinal luminal membrane that transports nutrients (imino/amino acids) and orally active neuromodulatory agents (used to treat affective disorders).

    Original languageEnglish
    Pages (from-to)1410-1422
    Number of pages13
    Issue number5
    Publication statusPublished - 2004


    Dive into the research topics of 'H+/amino acid transporter 1 (PAT1) is the imino acid carrier: an intestinal nutrient/drug transporter in human and rat'. Together they form a unique fingerprint.

    Cite this