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Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum.
Am J Physiol Gastrointest Liver Physiol. 2007 Oct; 293(4):G857-63.AJ

Abstract

Electroneutral Na absorption occurs in the intestine via sodium-hydrogen exchanger (NHE) isoforms NHE2 and NHE3. Bicarbonate and butyrate both stimulate electroneutral Na absorption through NHE. Bicarbonate- but not butyrate-dependent Na absorption is inhibited by cholera toxin (CT). Long-term exposure to butyrate also influences expression of apical membrane proteins in epithelial cells. These studies investigated the effects of short- and long-term in vivo exposure to butyrate on apical membrane NHE and mRNA, protein expression, and activity in rat ileal epithelium that had been exposed to CT. Ileal loops were exposed to CT in vivo for 5 h and apical membrane vesicles were isolated. 22Na uptake was measured by using the inhibitor HOE694 to identify NHE2 and NHE3 activity, and Western blot analyses were performed. CT reduced total NHE activity by 70% in apical membrane vesicles with inhibition of both NHE2 and NHE3. Reduced NHE3 activity and protein expression remained low following removal of CT but increased to control values following incubation of the ileal loop with butyrate for 2 h. In parallel there was a 40% decrease in CT-induced increase in cAMP content. In contrast, NHE2 activity partially increased following removal of CT and was further increased to control levels by butyrate. NHE2 protein expression did not parallel its activity. Neither NHE2 nor NHE3 mRNA content were affected by CT or butyrate. These results indicate that CT has varying effects on the two apical NHE isoforms, inhibiting NHE2 activity without altering its protein expression and reducing both NHE3 activity and protein expression. Butyrate restores both CT-inhibited NHE2 and NHE3 activities to normal levels but via different mechanisms.

Authors+Show Affiliations

Dept. of Internal Medicine, Yale Univ. School of Medicine, New Haven, CT 06520-8010, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17690171

Citation

Subramanya, Sandeep B., et al. "Differential Regulation of Cholera Toxin-inhibited Na-H Exchange Isoforms By Butyrate in Rat Ileum." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 293, no. 4, 2007, pp. G857-63.
Subramanya SB, Rajendran VM, Srinivasan P, et al. Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum. Am J Physiol Gastrointest Liver Physiol. 2007;293(4):G857-63.
Subramanya, S. B., Rajendran, V. M., Srinivasan, P., Nanda Kumar, N. S., Ramakrishna, B. S., & Binder, H. J. (2007). Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum. American Journal of Physiology. Gastrointestinal and Liver Physiology, 293(4), G857-63.
Subramanya SB, et al. Differential Regulation of Cholera Toxin-inhibited Na-H Exchange Isoforms By Butyrate in Rat Ileum. Am J Physiol Gastrointest Liver Physiol. 2007;293(4):G857-63. PubMed PMID: 17690171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential regulation of cholera toxin-inhibited Na-H exchange isoforms by butyrate in rat ileum. AU - Subramanya,Sandeep B, AU - Rajendran,Vazhaikkurichi M, AU - Srinivasan,Pugazhendhi, AU - Nanda Kumar,Navalpur S, AU - Ramakrishna,Balakrishnan S, AU - Binder,Henry J, Y1 - 2007/08/09/ PY - 2007/8/11/pubmed PY - 2007/12/6/medline PY - 2007/8/11/entrez SP - G857 EP - 63 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 293 IS - 4 N2 - Electroneutral Na absorption occurs in the intestine via sodium-hydrogen exchanger (NHE) isoforms NHE2 and NHE3. Bicarbonate and butyrate both stimulate electroneutral Na absorption through NHE. Bicarbonate- but not butyrate-dependent Na absorption is inhibited by cholera toxin (CT). Long-term exposure to butyrate also influences expression of apical membrane proteins in epithelial cells. These studies investigated the effects of short- and long-term in vivo exposure to butyrate on apical membrane NHE and mRNA, protein expression, and activity in rat ileal epithelium that had been exposed to CT. Ileal loops were exposed to CT in vivo for 5 h and apical membrane vesicles were isolated. 22Na uptake was measured by using the inhibitor HOE694 to identify NHE2 and NHE3 activity, and Western blot analyses were performed. CT reduced total NHE activity by 70% in apical membrane vesicles with inhibition of both NHE2 and NHE3. Reduced NHE3 activity and protein expression remained low following removal of CT but increased to control values following incubation of the ileal loop with butyrate for 2 h. In parallel there was a 40% decrease in CT-induced increase in cAMP content. In contrast, NHE2 activity partially increased following removal of CT and was further increased to control levels by butyrate. NHE2 protein expression did not parallel its activity. Neither NHE2 nor NHE3 mRNA content were affected by CT or butyrate. These results indicate that CT has varying effects on the two apical NHE isoforms, inhibiting NHE2 activity without altering its protein expression and reducing both NHE3 activity and protein expression. Butyrate restores both CT-inhibited NHE2 and NHE3 activities to normal levels but via different mechanisms. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/17690171/Differential_regulation_of_cholera_toxin_inhibited_Na_H_exchange_isoforms_by_butyrate_in_rat_ileum_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00462.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -