title: Characterization of CFTR High Expresser cells in the intestine.
abstract: The CFTR High Expresser (CHE) cells express eightfold higher levels of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel compared with neighboring enterocytes and were first identified by our laboratory (Ameen et al., Gastroenterology 108: 1016, 1995). We used double-label immunofluorescence microscopy to further study these enigmatic epithelial cells in rat intestine in vivo or ex vivo. CHE cells were found in duodenum, most frequent in proximal jejunum, and absent in ileum and colon. CFTR abundance increased in CHE cells along the crypt-villus axis. The basolateral Na(+)K(+)Cl(-) cotransporter NKCC1, a key transporter involved in Cl(-) secretion, was detected at similar levels in CHE cells and neighboring enterocytes at steady state. Microvilli appeared shorter in CHE cells, with low levels of Myosin 1a, a villus enterocyte-specific motor that retains sucrase/isomaltase in the brush-border membrane (BBM). CHE cells lacked alkaline phosphatase and absorptive villus enterocyte BBM proteins, including Na(+)H(+) exchanger NHE3, Cl(-)/HCO3(-) exchanger SLC26A6 (putative anion exchanger 1), and sucrase/isomaltase. High levels of the vacuolar-ATPase proton pump were observed in the apical domain of CHE cells. Levels of the NHE regulatory factor NHERF1, Na-K-ATPase, and Syntaxin 3 were similar to that of neighboring enterocytes. cAMP or acetylcholine stimulation robustly increased apical CFTR and basolateral NKCC1 disproportionately in CHE cells relative to neighboring enterocytes. These data strongly argue for a specialized role of CHE cells in Cl(-)-mediated "high-volume" fluid secretion on the villi of the proximal small intestine.
authors.affiliation: Dept. of Pediatrics/Gastroenterology and Hepatology, and Cellular and Molecular Physiology, Yale Univ. School of Medicine, P.O. Box 208064, 333 Cedar St, FMP 408, New Haven, CT 06520. nadia.ameen@yale.edu).
authors.forename: Robert L
authors.initials: RL
authors.lastname: Jakab
authors.forename: Anne M
authors.initials: AM
authors.lastname: Collaco
authors.forename: Nadia A
authors.initials: NA
authors.lastname: Ameen
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000648:ultrastructure; D007421:Intestine, Small / Q000166:cytology*; D008297:Male; D008871:Microvilli / Q000648:ultrastructure; D021381:Protein Transport / Q000187:drug effects; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D064506:Solute Carrier Family 12, Member 2 / Q000235:genetics / Q000378:metabolism
chemical_list: C579654:CFTR protein, rat; D050765:Qa-SNARE Proteins; C578879:Slc12a2 protein, rat; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D064506:Solute Carrier Family 12, Member 2; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine
keywords: Na+K+Cl- cotransporter 1; acetylcholine; camp-regulated traffic; cystic fibrosis transmembrane conductance regulator; villus enterocyte