Glutamine transporter in crypts compensates for loss of villus absorption in bovine cryptosporidiosis

Abstract

Cryptosporidium parvum infection represents a significant cause of diarrhea in humans and animals. We studied the effect of luminally applied glutamine and the PG synthesis inhibitor indomethacin on NaCl absorption from infected calf ileum in Ussing chambers. Infected ileum displayed a decrease in both mucosal surface area and NaCl absorption. Indomethacin and glutamine or its stable derivative alanyl-glutamine increased the net absorption of Na(+) in infected tissue in an additive manner and to a greater degree than in controls. Immunohistochemical and Western blot studies showed that in control animals neutral amino acid transport system ASC was present in villus and crypts, whereas in infected animals, ASC was strongly present only on the apical border of crypts. These results are consistent with PGs mediating the altered NaCl and water absorption in this infection. Our findings further illustrate that the combined use of a PG synthesis inhibitor and glutamine can fully stimulate Na(+) and Cl(-) absorption despite the severe villous atrophy, an effect associated with increased expression of a Na(+)-dependent amino acid transporter in infected crypts.

Effect of glutamine on water and sodium absorption in human jejunum at baseline and during PGE1-induced secretion

“…In the present study, an apparent stoichiometric ratio of about 1:1 for sodium-glucose and glutamine-glucose cotransport has been estimated, which is in accordance with classical experiments in rabbit ileum but probably underestimates the true absorptive glutamine:sodium ratio; other studies have suggested that a ratio of 2:1 was closer to the actual transepithelial influxes (3,5,13,20,29). Indeed, glutamine transport across intestinal brush-border membrane is only partly sodium dependent (36).…”

“…In these models, hypersecretion was induced by cholera toxin (1,24,37), cryptosporidiosis (2,5,10), rotavirus (33), or enteropathogenic Escherichia coli (29). In cholera-infected humans, glutamine in the presence of glucose reduced net water and sodium secretion to the same degree as glucose alone (41).…”

Enteric infections, diarrhea, and their impact on function and development

“…Because the major nutrient for this rapidly renewing epithelium is glutamine, it is not surprising that this provisionally essential amino acid becomes rate limiting for epithelial repair in malnourished individuals. The discovery that glutamine and its stable derivative, alanyl glutamine, drive not only epithelial repair but also electrogenic sodium absorption (even in the presence of villus damage) provides an attractive approach to ORNT (158)(159)(160)(161). Glutamine causes improvement that cannot be completely explained by enhanced fluid and Na absorption, and it seems to improve intestinal epithelial cell integrity and enhance tight junction function (162)(163)(164).…”

Drug treatment and novel drug target againstCryptosporidium

“…In animal models of Cryptosporidium and Rotavirus, glutamine has been shown to stimulate sodium reabsorption in the small intestine even in the context of bowel villous atrophy (Blikslager, 2001). …”