Cystic fibrosis transmembrane conductance regulator and Na+ channel subunits mRNA transcripts, and Cl− efflux, show a different distribution in rat duodenum and colon
We compared the distribution and putative association of Cl– channel transport, CFTR mRNA transcripts, and Na+ channel (ENaC)α- and β-subunit mRNA transcripts in villus and crypt epithelial cells of duodenum, with corresponding surface and crypt cells of colon from sodium-depleted rats. Methods:
Cells were loaded with 36Cl– and forskolin-stimulated efflux was determined. RT-PCR was performed for CFTR mRNA transcripts and ENaC α- and β-subunit mRNA. Duodenal epithelial cell response to VIP was assessed by measuring intracellular cAMP. Results:
Forskolin-stimulated Cl− efflux occurred with decreasing magnitude in duodenal crypt, duodenal villus, colonic crypt and colonic surface cells in Na+-depleted animals. CFTR expression was correlated directly with Cl− efflux (r = 0.91, P < 0.01). Na+ channel α-subunit was expressed in colon and duodenum in animals fed diets with a high or low sodium content. While the β-subunit mRNA was detected in the colon of sodium-restricted rats, it was absent in the duodenum under control conditions and after Na+ restriction. There was an inverse correlation between mRNA transcripts for CFTR and the ENaC α-subunit (r = −0.93, P < 0.003) and β-subunit (r = −0.91, P < 0.004) in colon. VIP-stimulated cAMP in duodenal epithelial cells was greater in crypt than villus (P < 0.05). Conclusion:
Cl− efflux, CFTR transcription and forskolin-stimulated cAMP activity occur in both crypt and villus epithelial cells in duodenum. Possible interaction between CFTR and Na+ channels is apparently limited to parts of the colonic crypt. Lack of duodenal β-subunit expression makes ENaC activity unlikely.
Document Type: Research Article
Affiliations: 1: Department of Gastroenterology, Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva, Israel 2: Biochemistry Institute of Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University, Rehovot, Israel 3: Department of Pathology, Sheba Medical Center and Tel Aviv University, Tel Hashomer, Israel 4: Gastroenterology Department, Rabin Medical Center and Tel Aviv University, Petah Tikva, Israel
Publication date: July 1, 2003