Abstract
Elevated levels of Na and Cl in airway surface liquid may play a major role in the airway pathology of cystic fibrosis (CF) (J. J. Smith, S. M. Travis, E. P. Greenberg, and M. J. Welsh. Cell 85: 229-236,1996) and could be caused by block of transcellular Cl absorption due to lack of a functional CF transmembrane conductance regulator (CFTR). To test for transcellular absorption of Cl across non-CF epithelium, we studied how fluid absorption was affected by the opening and closing of Cl channels. Forskolin (an activator of CFTR) tripled fluid absorption across primary cultures of bovine trachéal epithelium but had no effect on human cells. However, in both species, fluid absorption was markedly inhibited by 5-nitro-2-(3-phenylpropylamino)benzoate, a blocker of CFTR. Microelectrode studies suggested that the magnitude of the absorptive response to forskolin in bovine cells depended on the size of an inwardly directed electrochemical driving force for Cl movement across the apical membrane. Patch-clamp measurements of bovine cells revealed CFTR in the apical membrane and a cAMP-activated, inwardly rectifying Cl channel in the basolateral membrane. We conclude that a significant fraction of absorbed Cl passes transcellularly in bovine trachéal epithelial cultures, with CFTR as the path of entry in the apical membrane and a novel cAMPactivated Cl channel as the exit route in the basolateral membrane. Our data further indicate that a similar pathway may exist in non-CF human trachéal epithelium. adenosine 3′,5′-cyclic monophosphate; cystic fibrosis; airway surface liquid; epithelial ion transport
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology |
| Volume | 275 |
| Issue number | 6 PART 1 |
| State | Published - 1998 |
Fingerprint
ASJC Scopus subject areas
- Physiology (medical)
Cite this
CAMP-dependent absorption of chloride across airway epithelium. / Widdicombe, Jonathan.
In: American Journal of Physiology, Vol. 275, No. 6 PART 1, 1998.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - CAMP-dependent absorption of chloride across airway epithelium
AU - Widdicombe, Jonathan
PY - 1998
Y1 - 1998
N2 - Elevated levels of Na and Cl in airway surface liquid may play a major role in the airway pathology of cystic fibrosis (CF) (J. J. Smith, S. M. Travis, E. P. Greenberg, and M. J. Welsh. Cell 85: 229-236,1996) and could be caused by block of transcellular Cl absorption due to lack of a functional CF transmembrane conductance regulator (CFTR). To test for transcellular absorption of Cl across non-CF epithelium, we studied how fluid absorption was affected by the opening and closing of Cl channels. Forskolin (an activator of CFTR) tripled fluid absorption across primary cultures of bovine trachéal epithelium but had no effect on human cells. However, in both species, fluid absorption was markedly inhibited by 5-nitro-2-(3-phenylpropylamino)benzoate, a blocker of CFTR. Microelectrode studies suggested that the magnitude of the absorptive response to forskolin in bovine cells depended on the size of an inwardly directed electrochemical driving force for Cl movement across the apical membrane. Patch-clamp measurements of bovine cells revealed CFTR in the apical membrane and a cAMP-activated, inwardly rectifying Cl channel in the basolateral membrane. We conclude that a significant fraction of absorbed Cl passes transcellularly in bovine trachéal epithelial cultures, with CFTR as the path of entry in the apical membrane and a novel cAMPactivated Cl channel as the exit route in the basolateral membrane. Our data further indicate that a similar pathway may exist in non-CF human trachéal epithelium. adenosine 3′,5′-cyclic monophosphate; cystic fibrosis; airway surface liquid; epithelial ion transport
AB - Elevated levels of Na and Cl in airway surface liquid may play a major role in the airway pathology of cystic fibrosis (CF) (J. J. Smith, S. M. Travis, E. P. Greenberg, and M. J. Welsh. Cell 85: 229-236,1996) and could be caused by block of transcellular Cl absorption due to lack of a functional CF transmembrane conductance regulator (CFTR). To test for transcellular absorption of Cl across non-CF epithelium, we studied how fluid absorption was affected by the opening and closing of Cl channels. Forskolin (an activator of CFTR) tripled fluid absorption across primary cultures of bovine trachéal epithelium but had no effect on human cells. However, in both species, fluid absorption was markedly inhibited by 5-nitro-2-(3-phenylpropylamino)benzoate, a blocker of CFTR. Microelectrode studies suggested that the magnitude of the absorptive response to forskolin in bovine cells depended on the size of an inwardly directed electrochemical driving force for Cl movement across the apical membrane. Patch-clamp measurements of bovine cells revealed CFTR in the apical membrane and a cAMP-activated, inwardly rectifying Cl channel in the basolateral membrane. We conclude that a significant fraction of absorbed Cl passes transcellularly in bovine trachéal epithelial cultures, with CFTR as the path of entry in the apical membrane and a novel cAMPactivated Cl channel as the exit route in the basolateral membrane. Our data further indicate that a similar pathway may exist in non-CF human trachéal epithelium. adenosine 3′,5′-cyclic monophosphate; cystic fibrosis; airway surface liquid; epithelial ion transport
UR - http://www.scopus.com/inward/record.url?scp=33746694776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746694776&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:33746694776
VL - 275
JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology
SN - 1931-857X
IS - 6 PART 1
ER -