Stimulation of electrogenic intestinal dipeptide transport by the glucocorticoid dexamethasone

Rexhep Rexhepaj, Anand Rotte, Daniela S. Kempe, Mentor Sopjani, Michael Föller, Eva Maria Gehring, Madhuri Bhandaru, Ivonne Gruner, Andreas F. Mack, Isabel Rubio-Aliaga, Anna Maria Näßl, Hannelore Daniel, Dietmar Kuhl, Florian Lang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

According to recent in vitro experiments, the peptide transporter PepT2 is stimulated by the serum- and glucocorticoid-inducible kinase SGKl. The present study explored the contribution of SGK1 to the regulation of electrogenic intestinal peptide transport. Intestinal PepT1 was expressed in Xenopus oocytes, and peptide transport was determined by dual electrode voltage clamping. Peptide transport in intestinal segments was determined utilizing Ussing chamber. Cytosolic pH (pHi) was determined by BCECF fluorescence and Na+ZH+ exchanger activity was estimated from Na+-dependent pH recovery (ΔpHi) following an ammonium pulse. In PepT1-expressing Xenopus oocytes, coexpression of SGK1 enhanced electrogenie peptide transport. Intestinal transport and pHi of untreated mice were similar in SGK1 knockout mice (sgkl-/-) and their wild-type littermates (sgkl+/+). Glucocorticoid treatment (4 days 10 μg/g body weight (bw)/day dexamethasone) increased peptide transport in sgk1+//+ but not in sgk1-/- mice. Irrespective of dexamethasone treatment, luminal peptide (5 mM glycyl-glycine) led to a similar early decrease of pHi in sgk1+/+ and sgk1+/+ mice, but to a more profound and sustained decline of pHi in sgk1-/- than in sgk1+/+ mice. In the presence and absence of glycyl-glycine, ΔpHi was significantly enhanced by dexamethasone treatment in sgk1+/+ mice, an effect significantly blunted in sgk1-/- mice. During sustained exposure to glycyl-glycine, ΔpHi was significantly larger in sgk1F+/+ mice than in sgk1-/- mice, irrespective of dexamethasone treatment. In conclusion, basal intestinal peptide transport does not require stimulation by SGK1. Glucocorticoid treatment stimulates both Na+/H+ exchanger activity and peptide transport, effects partially dependent on SGK1. Moreover, chronic exposure to glycyl-glycine stimulates Na+ZH+ exchanger activity, an effect again involving SGK1.

Original languageEnglish
Pages (from-to)191-202
Number of pages12
JournalPflugers Archiv European Journal of Physiology
Volume459
Issue number1
DOIs
StatePublished - Nov 2009

Keywords

  • Dexamethasone
  • Pept1
  • Serum- and glucocorticoid-inducible kinase

Fingerprint

Dive into the research topics of 'Stimulation of electrogenic intestinal dipeptide transport by the glucocorticoid dexamethasone'. Together they form a unique fingerprint.

Cite this