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Am J Physiol Gastrointest Liver Physiol (November 13, 2002). doi:10.1152/ajpgi.00292.2002
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Articles in PresS, published online ahead of print November 13, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00292.2002
Submitted on July 19, 2002
Accepted on October 31, 2002

Bile salts potentiate adenylyl cyclase activity and cAMP-regulated secretion in the human gallbladder epithelium

Nicolas Chignard1, Martine Mergey1, Danielle Veissiere1, Raoul Poupon2, Jacqueline Capeau3, Rolland Parc4, Annick Paul1, and Chantal Housset5*

1 Unite 402, Institut National de la Sante et de la Recherche Medicale, Paris, France
2 Unite 402, Institut National de la Sante et de la Recherche Medicale, Paris, France; Service d Hepatologie, Hopital Saint-Antoine, Paris, France
3 Unite 402, Institut National de la Sante et de la Recherche Medicale, Paris, France; Service de Biochimie, Hopital Tenon, Paris, France
4 Service de Chirurgie Generale et Digestive, Hopital Saint-Antoine, Paris, France
5 Unite 402, Institut National de la Sante et de la Recherche Medicale, Paris, France; Service d Hepatologie, Hopital Saint-Antoine, Paris, France; Service de Biochimie, Hopital Tenon, Paris, France

* To whom correspondence should be addressed. E-mail: chantal.housset{at}st-antoine.inserm.fr.

Fluid and ion secretion in the gallbladder is mainly triggered by the intracellular second messenger cAMP. We herein 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 following protein kinase C (PKC) inhibition, while both taurochenodeoxycholate and tauroursodeoxycholate induced PKC{alpha} and PKC{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. Cyclic AMP-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.




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