Bicarbonate secretion in the murine gallbladder--lessons for the treatment of cystic fibrosis.
The epithelium lining the gallbladder of mammalian species has absorptive and secretory functions. An important function is the secretion of a bicarbonate rich fluid that helps neutralise stomach acid and provides an appropriate environment for intestinal enzymes. In cystic fibrosis (CF) this secretory function is lost. This study concerns the bicarbonate secreting activity of murine gallbladders in vitro using wild type and CF mice and four main questions are considered as follows: a) Does the murine gallbladder secrete bicarbonate electrogenically and is this prevented in CF? b) Can the secretory activity in CF gallbladders be restored by gene therapy or pharmacologically? c) How is the cystic fibrosis transmembrane conductance regulator (CFTR) involved in bicarbonate secretion? d) Does the data offer prospects for the treatment of CF?. Work from both the author's laboratory and the literature will be reviewed. Consideration of the currently available data indicates that the wild type murine gallbladder does secrete bicarbonate electrogenically and that this is absent in CF mice. Further it has been demonstrated that bicarbonate secretory activity can be restored by both gene therapy and by the use of drugs. The role of CFTR in bicarbonate secretion remains equivocal. Much evidence suggests that CFTR can act as a channel for HCO(3)(-) ions as well as Cl(-) ions, while others propose a parallel arrangement of CFTR with a Cl(-)/HCO(3)(-) exchanger is necessary. The matter is further complicated by the regulatory role of CFTR on other transporting activities. Opportunities for possible application to man are discussed.
Cuthbert
A W
AW
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hill's Road, Cambridge, United Kingdom. awc1000@cam.ac.uk
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology; D004195:Disease Models, Animal; D005704:Gallbladder / Q000378:metabolism*; D018014:Gene Transfer Techniques / Q000009:adverse effects; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods; D006801:Humans; D051379:Mice; D010477:Perfusion / Q000379:methods
D001639:Bicarbonates; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator