Stimulation of electrogenic intestinal dipeptide transport by the glucocorticoid dexamethasone.
According to recent in vitro experiments, the peptide transporter PepT2 is stimulated by the serum- and glucocorticoid-inducible kinase SGK1. 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 (pH( i )) was determined by BCECF fluorescence and Na(+)/H(+) exchanger activity was estimated from Na(+)-dependent pH recovery (pH ( i )) following an ammonium pulse. In PepT1-expressing Xenopus oocytes, coexpression of SGK1 enhanced electrogenic peptide transport. Intestinal transport and pH( i ) of untreated mice were similar in SGK1 knockout mice (sgk1 ( -/- )) and their wild-type littermates (sgk1 ( +/+ )). Glucocorticoid treatment (4 days 10 microg/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 pH( i ) in sgk1 (-/-) and sgk1 (+/+) mice, but to a more profound and sustained decline of pH( i ) in sgk1 (-/-) than in sgk1 ( +/+ ) mice. In the presence and absence of glycyl-glycine, pH ( i ) was significantly enhanced by dexamethasone treatment in sgk1 ( +/+ ) mice, an effect significantly blunted in sgk1 ( -/- ) mice. During sustained exposure to glycyl-glycine, pH ( i ) was significantly larger in sgk1 (+/+) 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(+)/H(+) exchanger activity, an effect again involving SGK1.
Rexhepaj
Rexhep
R
Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076, Tübingen, Germany.
Rotte
Anand
A
Kempe
Daniela S
DS
Sopjani
Mentor
M
Föller
Michael
M
Gehring
Eva-Maria
EM
Bhandaru
Madhuri
M
Gruner
Ivonne
I
Mack
Andreas F
AF
Rubio-Aliaga
Isabel
I
Nässl
Anna-Maria
AM
Daniel
Hannelore
H
Kuhl
Dietmar
D
Lang
Florian
F
D000818:Animals; D003907:Dexamethasone / Q000378:metabolism*; D004151:Dipeptides / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000378:metabolism*; D006033:Glycylglycine / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D027981:Symporters / Q000378:metabolism*; D014981:Xenopus; D000099184:Serum-Glucocorticoid Regulated Kinases
D003907:Dexamethasone; D004151:Dipeptides; D005938:Glucocorticoids; D006033:Glycylglycine; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D017923:Sodium-Hydrogen Exchangers; D027981:Symporters; D000099184:Serum-Glucocorticoid Regulated Kinases; C093694:hydrogen-coupled oligopeptide transporter PepT2