AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 1 172-G180, Copyright © 1997 by American Physiological Society

ARTICLES

Characterization of two distinct chloride channels in cultured dog pancreatic duct epithelial cells

T. D. Nguyen, D. S. Koh, M. W. Moody, N. R. Fox, C. E. Savard, R. Kuver, B. Hille and S. P. Lee
Department of Medicine, University of Washington, Seattle, Washington 98108, USA. tlnguyen@u.washington.edu

Cl- secretion by pancreatic duct epithelial cells (PDEC) regulates cellular HCO3- secretion, an important component of the exocrine pancreas. In cystic fibrosis, for example, impaired function of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel results in decreased pancreatic secretion and secondary pancreatic insufficiency. Studies of ion transport by PDEC have been hindered by the lack of a practical in vitro model. We have successfully cultured nontransformed dog PDEC on Vitrogen-coated permeable membranes overlying a feeder layer of myofibroblasts and report the characterization of Cl- channels in these cells. Cl- conductance, assessed through efflux of 125I from PDEC, was stimulated by agents acting via adenosine 3',5'-cyclic monophosphate (cAMP) or cytosolic Ca2+. The Cl- conductances activated by cAMP and Ca2+ were distinct, since they were differentially inhibited by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid and, to a lesser extent, by 5-nitro-2-(3-phenylpropylamino)benzoic acid and diphenylamine-2 carboxylate. Patch-clamp studies confirmed the presence of Cl- channels activated by cAMP and Ca2+, with differential inhibition by 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid. The presence of CFTR Cl- channels in PDEC was confirmed by immunoblotting. These cultured PDEC are an optimal model for studies of pancreatic duct secretion.

This article has been cited by other articles:

				J. G. Kirkland, G. S. Cottrell, N. W. Bunnett, and C. U. Corvera Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G335 - G346. [Abstract] [Full Text] [PDF]

				C. Okolo, T. Wong, M. W. Moody, and T. D. Nguyen Effects of bile acids on dog pancreatic duct epithelial cell secretion and monolayer resistance Am J Physiol Gastrointest Liver Physiol, November 1, 2002; 283(5): G1042 - G1050. [Abstract] [Full Text] [PDF]

				T. D. Nguyen, S. Meichle, U. S. Kim, T. Wong, and M. W. Moody P2Y11, a purinergic receptor acting via cAMP, mediates secretion by pancreatic duct epithelial cells Am J Physiol Gastrointest Liver Physiol, May 1, 2001; 280(5): G795 - G804. [Abstract] [Full Text] [PDF]

				C. N. Fortner, J. N. Lorenz, and R. J. Paul Chloride channel function is linked to epithelium-dependent airway relaxation Am J Physiol Lung Cell Mol Physiol, February 1, 2001; 280(2): L334 - L341. [Abstract] [Full Text] [PDF]

				B. D. SCHULTZ, A. K. SINGH, D. C. DEVOR, and R. J. BRIDGES Pharmacology of CFTR Chloride Channel Activity Physiol Rev, January 1, 1999; 79(1): 109 - 144. [Abstract] [Full Text] [PDF]

				T. D. Nguyen, C. N. Okolo, and M. W. Moody Histamine stimulates ion transport by dog pancreatic duct epithelial cells through H1 receptors Am J Physiol Gastrointest Liver Physiol, July 1, 1998; 275(1): G76 - G84. [Abstract] [Full Text] [PDF]

				T. D. Nguyen, M. W. Moody, C. E. Savard, and S. P. Lee Secretory effects of ATP on nontransformed dog pancreatic duct epithelial cells Am J Physiol Gastrointest Liver Physiol, July 1, 1998; 275(1): G104 - G113. [Abstract] [Full Text] [PDF]