title: H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat.
abstract: OBJECTIVE
  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 N(+) /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 (N(+) /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).
authors.affiliation: Faculty of Medical Sciences, nUniversity of Newcastle Upon Tyne, Newcasttle Upon Tyne, UK.
authors.forename: Catriona M H
authors.initials: CM
authors.lastname: Anderson
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Grenade
authors.forename: Michael
authors.initials: M
authors.lastname: Boll
authors.forename: Martin
authors.initials: M
authors.lastname: Foltz
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Wake
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Lars K
authors.initials: LK
authors.lastname: Munck
authors.forename: Seiji
authors.initials: S
authors.lastname: Miyauchi
authors.forename: Peter M
authors.initials: PM
authors.lastname: Taylor
authors.forename: Frederick Charles
authors.initials: FC
authors.lastname: Campbell
authors.forename: Bjarne G
authors.initials: BG
authors.lastname: Munck
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
authors.forename: Vadivel
authors.initials: V
authors.lastname: Ganapathy
authors.forename: David T
authors.initials: DT
authors.lastname: Thwaites
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism*; D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D017931:DNA Primers; D005260:Female; D006801:Humans; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D009865:Oocytes / Q000502:physiology; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D051381:Rats; D027981:Symporters; D014982:Xenopus laevis
chemical_list: D026905:Amino Acid Transport Systems; D026921:Amino Acid Transport Systems, Neutral; D000596:Amino Acids; D017931:DNA Primers; C475905:SLC36A1 protein, human; C493537:Slc36a1 protein, rat; D027981:Symporters