title: Bile salts potentiate adenylyl cyclase activity and cAMP-regulated secretion in human gallbladder epithelium.
abstract: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Hôpital Saint-Antoine, 75012 Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chignard
authors.forename: Martine
authors.initials: M
authors.lastname: Mergey
authors.forename: Danielle
authors.initials: D
authors.lastname: Veissière
authors.forename: Raoul
authors.initials: R
authors.lastname: Poupon
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Rolland
authors.initials: R
authors.lastname: Parc
authors.forename: Annick
authors.initials: A
authors.lastname: Paul
authors.forename: Chantal
authors.initials: C
authors.lastname: Housset
mesh_terms: 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
chemical_list: 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