title: Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.
abstract: Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.
authors.affiliation: Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors.forename: Raphael N
authors.initials: RN
authors.lastname: Vuille-dit-Bille
authors.forename: Simone M
authors.initials: SM
authors.lastname: Camargo
authors.forename: Luca
authors.initials: L
authors.lastname: Emmenegger
authors.forename: Tom
authors.initials: T
authors.lastname: Sasse
authors.forename: Eva
authors.initials: E
authors.lastname: Kummer
authors.forename: Julia
authors.initials: J
authors.lastname: Jando
authors.forename: Qeumars M
authors.initials: QM
authors.lastname: Hamie
authors.forename: Chantal F
authors.initials: CF
authors.lastname: Meier
authors.forename: Schirin
authors.initials: S
authors.lastname: Hunziker
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Forras-Kaufmann
authors.forename: Sena
authors.initials: S
authors.lastname: Kuyumcu
authors.forename: Mark
authors.initials: M
authors.lastname: Fox
authors.forename: Werner
authors.initials: W
authors.lastname: Schwizer
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Maja
authors.initials: M
authors.lastname: Lindenmeyer
authors.forename: Oliver
authors.initials: O
authors.lastname: Götze
authors.forename: François
authors.initials: F
authors.lastname: Verrey
mesh_terms: D026921:Amino Acid Transport Systems, Neutral / Q000235:genetics* / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*; D014982:Xenopus laevis
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D000806:Angiotensin-Converting Enzyme Inhibitors; D026901:Membrane Transport Proteins; C491436:SLC6A19 protein, human; C431703:SLC6A20 protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2