Cftr expression and mucin secretion in cultured mouse gallbladder
epithelial cells.
Peters, Richard H. P. C., Pim J. French, J. Hikke Van Doorninck,
Genevieve Lamblin, Rosemary Ratcliff, Martin J. Evans, William H
Colledge, Jan Bijman, Bob J. Scholte.
Cell Biology, Erasmus University, PO box 1738, 3000 DR Rotterdam,
the Netherlands, Unite INSERM #377, 59045 Lille France, Wellcome/CRC,
Tennis Court Rd. Cambridge CB2, 1QR, UK
APStracts 3:0137G, 1996.
Dysfunction of the Cystic Fibrosis Transmembrane conductance Regulator
(CFTR) in humans is frequently associated with progressive liver
disease which appears to result from obstruction of biliary ducts
with mucous material. CFTR in the liver is expressed in the biliary
epithelium. Using a mouse model for cystic fibrosis (CF) we have
studied the relationship between CFTR expression and glycoprotein
secretion in primary culture of mouse gallbladder epithelial cells
(MGBC). MGBC in culture maintain a well differentiated phenotype as
shown by microscopy. The cells produce CFTR mRNA to levels comparable
to the intact tissue. With patch clamp analysis we could frequently
observe a linear protein kinase A regulated chloride channel which
shows all the major characteristics of human CFTR, although its
conductance is lower (5 pS compared to 8 pS). MGBC in culture produce
and secrete high molecular weight glycoproteins (HMG) in a time
dependent and temperature sensitive manner. Secretion of HMG was not
stimulated significantly by either cAMP, Ca2+ or protein kinase C
agonists in this system. High concentrations (3 mM) of extracellular
ATP stimulated secretion threefold but low concentrations (0.3 mM)
had no effect. Approximately one third of the HMG produced and
secreted consisted of mucin. Cultured MGBC from CFTR deficient mice
produced and secreted mucin to a similar extent as normal cells. We
conclude that cultured mouse gallbladder cells are a convenient model
to study both CFTR function and mucin secretion. In this system, we
found no evidence for a direct link between mucin secretion and CFTR
activity, as has been suggested for other
Received 1 February 1996; accepted in final form 10 July 1996.
APS Manuscript Number G45-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996