Bile salts potentiate adenylyl cyclase activity and cAMP-regulated secretion in human gallbladder epithelium.
Fluid and ion secretion in the gallbladder is mainly triggered by the intracellular second messenger cAMP. We examined the action of bile salts on the cAMP-dependent pathway in the gallbladder epithelium. Primary cultures of human gallbladder epithelial cells were exposed to agonists of the cAMP pathway and/or to bile salts. Taurochenodeoxycholate and tauroursodeoxycholate increased forskolin-induced cAMP accumulation to a similar extent, without affecting cAMP basal levels. This potentiating effect was abrogated after PKC inhibition, whereas both taurochenodeoxycholate and tauroursodeoxycholate induced PKC-alpha and -delta translocation to cell membranes. Consistent with a PKC-mediated stimulation of cAMP production, the expression of six adenylyl cyclase isoforms, including PKC-regulated isoforms 5 and 7, was identified in human gallbladder epithelial cells. cAMP-dependent chloride secretion induced by isoproterenol, a beta-adrenergic agonist, was significantly increased by taurochenodeoxycholate and by tauroursodeoxycholate. In conclusion, endogenous and therapeutic bile salts via PKC regulation of adenylyl cyclase activity potentiate cAMP production in the human gallbladder epithelium. Through this action, bile salts may increase fluid secretion in the gallbladder after feeding.
Chignard
Nicolas
N
Institut National de la Santé et de la Recherche Médicale, Hôpital Saint-Antoine, 75012 Paris, France.
Mergey
Martine
M
Veissière
Danielle
D
Poupon
Raoul
R
Capeau
Jacqueline
J
Parc
Rolland
R
Paul
Annick
A
Housset
Chantal
C
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005704:Gallbladder / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007118:Immunoassay; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001647:Bile Acids and Salts; D002712:Chlorides; D007527:Isoenzymes; D012333:RNA, Messenger; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D000242:Cyclic AMP; D011493:Protein Kinase C; D000262:Adenylyl Cyclases; D007545:Isoproterenol