scholarly journals Interleukin-13 (IL-13)/IL-13 Receptor α1 (IL-13Rα1) Signaling Regulates Intestinal Epithelial Cystic Fibrosis Transmembrane Conductance Regulator Channel-dependent Cl−Secretion

2011 ◽  
Vol 286 (15) ◽  
pp. 13357-13369 ◽  
Author(s):  
David Wu ◽  
Richard Ahrens ◽  
Heather Osterfeld ◽  
Taeko K. Noah ◽  
Katherine Groschwitz ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Intestinal Epithelial ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cl Secretion ◽  
Interleukin 13 ◽  
Channel Dependent ◽  
Cystic Fibrosis Transmembrane

cAMP- but not Ca(2+)-regulated Cl- conductance is lacking in cystic fibrosis mice epididymides and seminal vesicles

1996 ◽  
Vol 271 (1) ◽  
pp. C188-C193 ◽  
Author(s):  
A. Y. Leung ◽  
P. Y. Wong ◽  
J. R. Yankaskas ◽  
R. C. Boucher
Keyword(s):  
Cystic Fibrosis ◽  
Secretory Pathway ◽  
Short Circuit ◽  
Primary Cultures ◽  
Seminal Vesicles ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Cl Secretion ◽  
Induced Changes ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) reflects the loss of adenosine 3',5'-cyclic monophosphate (cAMP)-regulated Cl- secretion consequent to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In humans, but not mice, with CF, the disease is associated with male infertility. The present study investigated the relative magnitudes of the cAMP pathways and an alternative Ca(2+)-regulated Cl- secretory pathway in primary cultures of the epididymides and the seminal vesicles of normal and CF mice. The basal equivalent short-circuit currents (Ieq) of cultures derived from the epididymides and the seminal vesicles from the CF mice were lower (6.0 +/- 0.6 and 4.0 +/- 1.0 muA/cm2, respectively) than those from normal mice (11.1 +/- 1.0 and 6.6 +/- 0.6 muA/cm2, respectively). Forskolin induced significant Ieq responses in both the epididymis (8.0 +/- 0.7 muA/cm2) and seminal vesicles (4.0 +/- 0.5 muA/cm2) from normal mice, whereas forskolin-induced changes in Ieq in CF mouse epididymis and seminal vesicles were absent, consistent with defective cAMP-CFTR-mediated Cl- secretion in CF mice. Ieq responses to agonists (ionomycin, ATP) that raise intracellular Ca2+ (Ca2+i) were larger than forskolin responses in normal animals (6.6 +/- 0.9 and 13.4 +/- 1.8 muA/cm2, respectively) and were preserved in CF (6.5 +/- 0.9 and 17.1 +/- 1.0 muA/cm2, respectively). We speculate that the fertility of male CF mice is maintained by persistent expression of the predominant alternative Ca(2+)-mediated Cl- transport system in the epididymides and seminal vesicles.

scholarly journals Bicarbonate and Chloride Secretion in Calu-3 Human Airway Epithelial Cells

1999 ◽  
Vol 113 (5) ◽  
pp. 743-760 ◽  
Author(s):  
Daniel C. Devor ◽  
Ashvani K. Singh ◽  
Linda C. Lambert ◽  
Arthur DeLuca ◽  
Raymond A. Frizzell ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Basolateral Membrane ◽  
Disulfonic Acid ◽  
Transmembrane Conductance Regulator ◽  
Submucosal Gland ◽  
Transmembrane Conductance ◽  
Cl Secretion ◽  
Human Airway ◽  
Serous Cell ◽  
Cystic Fibrosis Transmembrane

Serous cells are the predominant site of cystic fibrosis transmembrane conductance regulator expression in the airways, and they make a significant contribution to the volume, composition, and consistency of the submucosal gland secretions. We have employed the human airway serous cell line Calu-3 as a model system to investigate the mechanisms of serous cell anion secretion. Forskolin-stimulated Calu-3 cells secrete HCO−3 by a Cl −-independent, serosal Na+-dependent, serosal bumetanide-insensitive, and serosal 4,4′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive, electrogenic mechanism as judged by transepithelial currents, isotopic fluxes, and the results of ion substitution, pharmacology, and pH studies. Similar studies revealed that stimulation of Calu-3 cells with 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of basolateral membrane Ca2+-activated K+ channels, reduced HCO−3 secretion and caused the secretion of Cl − by a bumetanide-sensitive, electrogenic mechanism. Nystatin permeabilization of Calu-3 monolayers demonstrated 1-EBIO activated a charybdotoxin- and clotrimazole- inhibited basolateral membrane K+ current. Patch-clamp studies confirmed the presence of an intermediate conductance inwardly rectified K+ channel with this pharmacological profile. We propose that hyperpolarization of the basolateral membrane voltage elicits a switch from HCO−3 secretion to Cl − secretion because the uptake of HCO−3 across the basolateral membrane is mediated by a 4,4 ′-dinitrostilben-2,2′-disulfonic acid (DNDS)–sensitive Na+:HCO−3 cotransporter. Since the stoichiometry reported for Na +:HCO−3 cotransport is 1:2 or 1:3, hyperpolarization of the basolateral membrane potential by 1-EBIO would inhibit HCO−3 entry and favor the secretion of Cl −. Therefore, differential regulation of the basolateral membrane K+ conductance by secretory agonists could provide a means of stimulating HCO−3 and Cl − secretion. In this context, cystic fibrosis transmembrane conductance regulator could serve as both a HCO−3 and a Cl − channel, mediating the apical membrane exit of either anion depending on basolateral membrane anion entry mechanisms and the driving forces that prevail. If these results with Calu-3 cells accurately reflect the transport properties of native submucosal gland serous cells, then HCO−3 secretion in the human airways warrants greater attention.

Ion transport across the jejunum in normal and cystic fibrosis mice

1995 ◽  
Vol 268 (3) ◽  
pp. G505-G513 ◽  
Author(s):  
B. R. Grubb
Keyword(s):  
Cystic Fibrosis ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Fluid Secretion ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Targeted Disruption ◽  
Cl Secretion ◽  
Ion Substitution ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) mice created by targeted disruption of the murine cystic fibrosis transmembrane conductance regulator gene lack adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- secretion and exhibit marked intestinal complications secondary to inadequate fluid secretion. The basal short-circuit current (Isc) in the normal murine jejuna [43.2 +/- 5.9 microA.cm-2, n = 10 (mean +/- SE)] exhibits marked spontaneous n = 10 (mean +/- SE)] exhibits marked spontaneous oscillations (amplitude = 47.9 microA.cm-2, n = 18), which were completely absent in the CF jejunum. Treatment of normal jejuna with the neuronal blocker tetrodotoxin completely eliminated the oscillations and decreased the Isc to levels not significantly different from the low basal Isc (5.4 +/- 2.8 microA.cm-2, n = 16) exhibited by CF tissue. Ion substitution studies revealed basal Isc in normal jejuna to be due primarily to Cl- secretion but these tissues appeared to be capable of HCO3- secretion as well. In contrast, CF jejuna spontaneously secreted neither Cl- nor HCO3-, which may indicate that CF jejuna have a defect in the ability to secrete both of these anions. Apical glucose elicited an electrogenic absorption of Na+ of identical magnitude in normal and CF jejuna. Without apical glucose, CF jejuna exhibited a very small Isc response to forskolin (delta 2.2 +/- 0.67 microA.cm-2, n = 10). However, in the presence of apical glucose, forskolin elicited an eightfold greater Isc response in the CF tissue (delta 17.2 +/- 4.8 microA.cm-2, n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Genistein activates CFTR-mediated Cl−secretion in the murine trachea and colon

2000 ◽  
Vol 279 (2) ◽  
pp. C383-C392 ◽  
Author(s):  
Catharine A. Goddard ◽  
Martin J. Evans ◽  
William H. Colledge
Keyword(s):  
Cystic Fibrosis ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Transmembrane Conductance Regulator ◽  
Wild Type ◽  
Transmembrane Conductance ◽  
Cell Systems ◽  
Cl Secretion ◽  
Cystic Fibrosis Transmembrane

The action of the isoflavone genistein on the cystic fibrosis transmembrane conductance regulator (CFTR) has been studied in many cell systems but not in intact murine tissues. We have investigated the action of genistein on murine tissues from normal and cystic fibrosis (CF) mice. Genistein increased the short-circuit current ( I sc) in tracheal (16.4 ± 2.8 μA/cm2) and colonic (40.0 ± 4.4 μA/cm2) epithelia of wild-type mice. This increase was inhibited by furosemide, diphenylamine-2-carboxylate, and glibenclamide, but not by DIDS. In contrast, genistein produced no significant change in the I sc of the tracheal epithelium (0.9 ± 1.1 μA/cm2) and decreased the I sc of colons from CF null (−13.1 ± 2.3 μA/cm2) and ΔF508 mice (−10.3 ± 1.3 μA/cm2). Delivery of a human CFTRcDNA-liposome complex to the airways of CF null mice restored the genistein response in the tracheas to wild-type levels. Tracheas from ΔF508 mice were also studied: 46% of trachea showed no response to genistein, whereas 54% gave an increase in I scsimilar to that in wild type. We conclude that genistein activates CFTR-mediated Cl− secretion in the murine trachea and distal colon.

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