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.