Am J Physiol Cell Physiol Information on EB 2010
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol 280: C296-C302, 2001;
0363-6143/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Merlin, D.
Right arrow Articles by Madara, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Merlin, D.
Right arrow Articles by Madara, J. L.
Vol. 280, Issue 2, C296-C302, February 2001

Cryptdin-3 induces novel apical conductance(s) in Clminus secretory, including cystic fibrosis, epithelia

Didier Merlin1, Gang Yue2, Wayne I. Lencer3, Michael E. Selsted4, and James L. Madara1

1 Department of Pathology and 2 Center for Cell and Molecular Signaling, Emory University School of Medicine, Atlanta, Georgia 30322; 3 Combined Program in Pediatric Gastroenterology and Nutrition, Department of Medicine, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115; and 4 Department of Pathology, University of California College of Medicine, Irvine, California 92717

Opening of anion-conductive pathways in apical membranes of secretory cells lining mucosal surfaces is a critical step in salt and water secretion and, thus, hydration of sites including airway and intestine. In intestine, Paneth cells are positioned at the base of the secretory gland (crypt) and release defensin peptide, in mice termed cryptdins, into the crypt lumen. Because at least some defensins have been shown to form anion-conductive channels in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes. To directly evaluate the possibility of cryptdin-3-mediated apical anion conductance (Gap), we have utilized amphotericin B to selectively permeabilize basolateral membranes of electrically tight monolayers of polarized human intestinal secretory epithelia (T84 cells), thus isolating the apical membrane for study. Cryptdin-3 induces Gap that is voltage independent (Delta Gap = 1.90 ± 0.60 mS/cm2) and exhibits ion selectivity contrasting to that elicited by forskolin or thapsigargin (for cryptdin-3, Cl- = gluconate; for forskolin and thapsigargin, Cl- gluconate). We cannot exclude the possibility that the macroscopic current induced by cryptdin could be the sum of cation and Cl- currents. Cryptdin-3 induces a current in basolaterally permeabilized epithelial monolayers derived from airway cells harboring the Delta F508 mutation of cystic fibrosis (CF; Delta Gap = 0.80 ± 0.06 mS/cm2), demonstrating that cryptdin-3 restores anion secretion in CF cells; this occurs independently of the CF transmembrane conductance regulator channel. These results support the idea that cryptdin-3 may associate with apical membranes of Cl--secreting epithelia and self-assemble into conducting channels capable of mediating a physiological response.

intestinal epithelium; conducting channels; amphotericin B


This article has been cited by other articles:


Home page
 J. Virol.Home page
H. Tanabe, A. J. Ouellette, M. J. Cocco, and W. E. Robinson Jr.
Differential Effects on Human Immunodeficiency Virus Type 1 Replication by {alpha}-Defensins with Comparable Bactericidal Activities
J. Virol., November 1, 2004; 78(21): 11622 - 11631.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
D. M. Hoover, Z. Wu, K. Tucker, W. Lu, and J. Lubkowski
Antimicrobial Characterization of Human {beta}-Defensin 3 Derivatives
Antimicrob. Agents Chemother., September 1, 2003; 47(9): 2804 - 2809.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
K. Kunzelmann and M. Mall
Electrolyte Transport in the Mammalian Colon: Mechanisms and Implications for Disease
Physiol Rev, January 1, 2002; 82(1): 245 - 289.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. T. Abreu, E. T. Arnold, J. Y. C. Chow, and K. E. Barrett
Phosphatidylinositol 3-Kinase-dependent Pathways Oppose Fas-induced Apoptosis and Limit Chloride Secretion in Human Intestinal Epithelial Cells. IMPLICATIONS FOR INFLAMMATORY DIARRHEAL STATES
J. Biol. Chem., December 7, 2001; 276(50): 47563 - 47574.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
G. Yue, D. Merlin, M. E. Selsted, W. I. Lencer, J. L. Madara, and D. C. Eaton
Cryptdin 3 forms anion selective channels in cytoplasmic membranes of human embryonic kidney cells
Am J Physiol Gastrointest Liver Physiol, May 1, 2002; 282(5): G757 - G765.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online