Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul;54(7):1001-1011.
doi: 10.1007/s00726-022-03154-4. Epub 2022 Apr 6.

Hypertension alters the function and expression profile of the peptide cotransporters PEPT1 and PEPT2 in the rodent renal proximal tubule

Othman A Alghamdi  1 , Nicola King  2 , Nicholas M Andronicos  3 , Graham L Jones  3 , Belal Chami  4 , Paul K Witting  5 , Pierre D J Moens  3
Affiliations

Hypertension alters the function and expression profile of the peptide cotransporters PEPT1 and PEPT2 in the rodent renal proximal tubule

Othman A Alghamdi et al. Amino Acids. 2022 Jul.

Abstract

Hypertension is a major risk factor for kidney and cardiovascular disease. The treatment of hypertensive individuals by selected ACE inhibitors and certain di-and tripeptides halts the progression of renal deterioration and extends life-span. Renal reabsorption of these low molecular weight substrates are mediated by the PEPT1 and PEPT2 cotransporters. This study aims to investigate whether hypertension and ageing affects renal PEPT cotransporters at gene, protein expression and distribution as well as function in the superficial cortex and the outer medulla of the kidney. Membrane vesicles from the brush border (BBMV) and outer medulla (OMMV) were isolated from the kidneys of young Wistar Kyoto (Y-WKY), young spontaneously hypertensive (Y-SHR), and middle aged SHR (M-SHR) rats. Transport activity was measured using the substrate, β-Ala-Lys (AMCA). Gene expression levels of PEPT genes were assessed with qRT-PCR while renal localisation of PEPT cotransporters was examined by immunohistochemistry with Western Blot validation. The Km and Vmax of renal PEPT1 were decreased significantly in SHR compared to WKY BBMV, whilst the Vmax of PEPT2 showed differences between SHR and WKY. By contrast to the reported cortical distribution of PEPT1, PEPT1-staining was detected in the outer medulla, whilst PEPT2 was expressed primarily in the cortex of all SHR; PEPT1 was significantly upregulated in the cortex of Y-SHR. These outcomes are indicative of a redistribution of PEPT1 and PEPT2 in the kidney proximal tubule under hypertensive conditions that has potential repercussions for nutrient handling and the therapeutic use of ACE inhibitors in hypertensive individuals.

Keywords: Ageing; Di- and tripeptides; Hypertension; PEPT1 and PEPT2.

PubMed Disclaimer

References

    1. Akarawut W, Lin CJ, Smith DE (1998) Noncompetitive inhibition of glycylsarcosine transport by quinapril in rabbit renal brush border membrane vesicles: effect on high-affinity peptide transporter. J Pharmacol Exptl Therapeut 287:684–690
    1. Alghamdi OA, King N, Jones GL, Moens PDJ (2017a) Kinetic measurements of Di- and tripeptide and peptidomimetic drug transport in different kidney regions using the fluorescent membrane potential-sensitive dye, DiS-C3-(3). J Membr Biol 250:641–649 - DOI
    1. Alghamdi OA, King N, Jones GL, Moens PDJ (2017b) A new use of beta-Ala-Lys (AMCA) as a transport reporter for PEPT1 and PEPT2 in renal brush border membrane vesicles from the outer cortex and outer medulla. Biochim Biophys Acta 1860:960–964 - DOI
    1. Alghamdi OA, King N, Andronicos NM, Jones GL, Chami B, Witting PK, Moens PDJ (2018) Molecular changes to the rat renal transporters PEPT1 and PEPT2 due to ageing. Mol Cell Biochem 452:71–82 - DOI
    1. Brandsch M, Knutter I, Bosse-Doenecke E (2008) Pharmaceutical and pharmacological importance of peptide transporters. J Pharmacy Pharmacol 60:543–585 - DOI

LinkOut - more resources