Phosphoinositide 3-kinase is involved in the glucagon-induced translocation of aquaporin-8 to hepatocyte plasma membrane |
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Authors: | Gradilone Sergio A Carreras Flavia I Lehmann Guillermo L Marinelli Raúl A |
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Affiliation: | Instituto de Fisiología Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 570, 2000 Rosario, Santa Fe, Argentina. |
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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. |
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Keywords: | bile secretion LY294002 membrane water permeability vesicle trafficking wortmannin |
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