Phosphoinositide 3-kinase is involved in the glucagon-induced translocation of aquaporin-8 to hepatocyte plasma membrane

Sergio A. Gradilone, Flavia I. Carreras, Guillermo L. Lehmann, Raúl A. Marinelli

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Background information. PI3K (phosphoinositide 3-kinase) mediates several signal transduction pathways in hepatocytes, including some involved in the regulation of vesicle trafficking. Hepatocytes express the water channel AQP8 (aquaporin-8) predominantly in an intracellular location, and it redistributes to the canalicular membrane, upon stimulation with the hormone glucagon, by a cAMP/protein kinase A-dependent mechanism. Since glucagon is capable of stimulating PI3K activity in hepatocytes and a cross talk between cAMP and PI3K has been suggested, in the present study, we examine whether PI3K activation is involved in the glucagon-induced translocation of AQP8. Results. By quantitative immunoblotting of purified hepatocyte plasma membranes, we found that the preincubation of cells with two structurally different PI3K inhibitors, wortmannin or LY294002, prevented the glucagon-induced translocation of AQP8 to hepatocyte plasma membrane. Confocal immunofluorescence microscopy in cultured hepatocytes confirmed the dependence of the hormone-induced redistribution of AQP8 on PI3K activity. Functional studies showed that the PI3K inhibitors were also capable of preventing the glucagon-induced increase in hepatocyte osmotic membrane water permeability. Conclusions. Our results suggest that PI3K activation is involved in the glucagon-dependent signal transduction pathways leading to hepatocyte AQP8 translocation.

Original languageEnglish (US)
Pages (from-to)831-836
Number of pages6
JournalBiology of the Cell
Volume97
Issue number11
DOIs
StatePublished - Nov 1 2005

Keywords

  • Bile secretion
  • LY294002
  • Membrane water permeability
  • Vesicle trafficking
  • Wortmannin

ASJC Scopus subject areas

  • Cell Biology

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