Cholestatic bile acids inhibit gap junction permeability in rat hepatocyte couplets and normal rat cholangiocytes.
OBJECTIVE
The aim of this work was to study the effects of different bile acids on the permeability of gap junction channels (PGJC). We also looked at the effects of some bile acids on the coordination of intercellular calcium oscillations.


METHODS
The permeability of gap junctions was assessed by fluorescent dye transfer and calcium signalling on fluorescent microscopy.


RESULTS
Cholestatic bile acids such as taurolithocholate, taurolithocholate-sulfate and taurochenodeoxycholate inhibit the permeability of gap junctions in a dose-dependent and reversible manner in hepatocytes. Experiments performed in other cell types suggest that this effect is specific for cells having bile salt transporters, independently of the type of connexin expressed in these cells. Thus, cholestatic bile acids inhibit PGJC in normal rat cholangiocytes which express Cx43, but not in HeLa cells transfected with Cx26 or 32, which are expressed in hepatocytes. Calcium oscillations induced by bile acids in rat hepatocyte couplets are not coordinated and, by inhibiting the PGJC, cholestatic bile acids prevent the coordination of calcium oscillations induced by noradrenaline in these cells.


CONCLUSIONS
Cholestatic, but not choleretic bile acids inhibit the PGJC in cells able to accumulate bile acids. This inhibition might contribute to the cholestatic effect of these bile acids.
Boucherie
Sylviane
S
INSERM. U442, Bâtiment 443, Université Paris-Sud, 15 rue Georges Clémenceau, 91405 Orsay cedex, France. sylviane.boucherie@ibaic.u-psud.fr
Koukoui
Omédine
O
Nicolas
Valérie
V
Combettes
Laurent
L
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology*; D002779:Cholestasis; D000072259:Connexin 26; D017630:Connexins; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013658:Taurolithocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D013655:Taurochenodeoxycholic Acid; D013658:Taurolithocholic Acid; D002118:Calcium