| Autor: |
Mingmin Chen, Singh, Anurag, Fang Xiao, Dringenberg, Ulrike, Jian Wang, Engelhardt, Regina, Yeruva, Sunil, Rubio-Aliaga, Isabel, Näßl, Anna-Maria, Kottra, Gabor, Daniel, Hannelore, Seidler, Ursula |
| Předmět: |
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| Zdroj: |
American Journal of Physiology: Gastrointestinal & Liver Physiology; Jul2010, Vol. 299, pG265-G274, 10p, 3 Diagrams, 1 Chart, 7 Graphs |
| Abstrakt: |
PEPT1 function in mouse intestine has not been assessed by means of electrophysiology and methods to assess its role in intracellular pH and fluid homeostasis. Therefore, the effects of the dipeptide glycilsarcosin (Gly-Sar) on jejunal fluid absorption ad villous enterocyte intracellular pH (pHi) in vivo, as well as on enterocyte[14C]Gly-Sar uptake, short-circuit current (Isc) response, and enterocyte pHi in vitro were determined in wild-type and PEPT1-deficient mice and in mice lacking PEPT1. Immunohistochemistry for PEPT1 failed to detect any protein in enterocyte apical membranes in Slc15Sal-/- animals. Saturable Gly-Sar uplake in Slc15al-/- everted sac preparations was no longer detectable. Similarly, Gly-Sar-induced jejunal Isc response in vitro was abolished. The dipeptide-induced increase in fluid absorption in vivo was also abolished in animals lacking PEPT1. Since PEPT1 acts as an acid loader in enterocytes, enterocyte pHi was measured in vivo by two-photon in SNARF-4-loaded villous enterocytes of exteriorized jejuni in anesthetized mice, as well as in BCECF-loaded enterocytes of microdissected jejunal villi. Gly-Sar-induced pHi decrease was no longer observed in the absence of PEPT1. A reversal of the proton gradient across the luminal membrane did not significantly diminish Gly-Sar-induced Isc response, whereas a depolarization of the apical membrane potential by high K+ or via Na+-K+ -ATPase inhibition strongly diminished Gly-Sar-induced Isc responses. This study demonstrates for the for time that proton-coupled electrogenic dipeptide uptake in the native small intestine, mediated by PEPT1, relies on the negative apical membrane potential as the major driving force and contributes significantly to intestinal fluid transport. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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