HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/1/G279    most recent 00488.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Tuo, B.-G. Articles by Seidler, U. Search for Related Content PubMed PubMed Citation Articles by Tuo, B.-G. Articles by Seidler, U.

HORMONES AND SIGNALING

Phosphatidylinositol 3-kinase is involved in prostaglandin E₂-mediated murine duodenal bicarbonate secretion

¹Department of Gastroenterology and Hepatology, Hannover Medical School, Hannover, Germany; and ²Department of Gastroenterology, Affiliated Hospital, Zunyi Medical College, Zunyi, China

Submitted 20 October 2006 ; accepted in final form 12 April 2007

Prostaglandin E₂ (PGE₂) plays an important role in the regulation of duodenal bicarbonate (HCO₃^–) secretion, but its signaling pathway(s) are not fully understood. In the present study, we investigated the signaling pathways involved in PGE₂-mediated duodenal HCO₃^– secretion. Murine duodenal mucosal HCO₃^– secretion was examined in vitro in Ussing chambers by pH-stat titration in the presence of a variety of signal transduction modulators. Phosphatidylinositol 3-kinase (PI3K) activity was measured by immunoprecipitation of PI3K and ELISA, and Akt phosphorylation was measured by Western analysis with anti-phospho-Akt and anti-Akt antibodies. PGE₂-stimulated duodenal HCO₃^– secretion was reduced by the cAMP-dependent signaling pathway inhibitors MDL-12330A and KT-5720 by 23% and 20%, respectively; the Ca²⁺-influx inhibitor verapamil by 26%; and the calmodulin antagonist W-13 by 24%; whereas the PI3K inhibitors wortmannin and LY-294002 reduced PGE₂-stimulated HCO₃^– secretion by 51% and 47%, respectively. Neither the MAPK inhibitor PD-98059 nor the tyrosine kinase inhibitor genistein altered PGE₂-stimulated HCO₃^– secretion. PGE₂ application caused a rapid and concentration-dependent increase in duodenal mucosal PI3K activity and Akt phosphorylation. These results demonstrated that PGE₂ activates PI3K in duodenal mucosa and stimulates duodenal HCO₃^– secretion via cAMP-, Ca²⁺-, and PI3K-dependent signaling pathways.

intestine; EP receptor

This article has been cited by other articles:

				M. Sjoblom, A. K. Singh, W. Zheng, J. Wang, B.-g. Tuo, A. Krabbenhoft, B. Riederer, G. Gros, and U. Seidler Duodenal acidity "sensing" but not epithelial HCO3- supply is critically dependent on carbonic anhydrase II expression PNAS, August 4, 2009; 106(31): 13094 - 13099. [Abstract] [Full Text] [PDF]

				B. Tuo, G. Wen, Y. Zhang, X. Liu, X. Wang, X. Liu, and H. Dong Involvement of phosphatidylinositol 3-kinase in cAMP- and cGMP-induced duodenal epithelial CFTR activation in mice Am J Physiol Cell Physiol, January 1, 2009; 297(3): C503 - C515. [Abstract] [Full Text] [PDF]

				F. Pierucci-Alves and B. D. Schultz Bradykinin-Stimulated Cyclooxygenase Activity Stimulates Vas Deferens Epithelial Anion Secretion In Vitro in Swine and Humans Biol Reprod, September 1, 2008; 79(3): 501 - 509. [Abstract] [Full Text] [PDF]