Abstract

Preliminary results by our group showed that exposure to Rosiglitazone (RGZ) induces phosphorylation and apical translocation of AQP2 in mouse collecting duct clone 4 (MCD4) cells. Here we studied the effect of short-term exposure to 50 µM RGZ on cAMP- and Ca2+-mediated signaling pathways, both key players for AQP2-mediated water reabsorption in the collecting duct. Cytosolic Ca2+ and cAMP levels were imaged in real-time in MCD4 cells loaded with Fura-2 or transiently transfected with the EPAC-based fluorescent probe H90, respectively. Physiologically, AQP2 phosphorylation/translocation depends on cytosolic cAMP levels. Nonetheless, cAMP measurements showed that RGZ did not induce significant changes in cAMP levels. Conversely, 20 minutes RGZ stimulation of Fura-2 loaded MCD4 cells induced a large, transient cytosolic Ca2+ peak that was not the result of direct blockade of the SERCA pump since the rate of store empting elicited by CPA in the absence of external Ca2+ was not significantly different in the presence of RGZ. Importantly, removal of external Ca2+ and inhibition of Ca2+ channels with ruthenium red prevented the RGZ-induced increase in cytosolic Ca2+ indicating a prominent role for Ca2+ entry at the plasma membrane. In conclusion, RGZ-induced AQP2 phosphorylation/translocation process is likely initiated by a fast, large extracellular Ca2+ influx most likely via Ca2+-dependent transient receptor potential channels. Further studies to ascertain which cascade of kinases is involved in this scenario are in progress.

Autore Pugliese

• Gerbino Andrea , Procino Giuseppe

Tutti gli autori

• GERBINO A.;PROCINO G.;SVELTO M.

Titolo volume/Rivista

Non Disponibile

Anno di pubblicazione

2014

ISSN

0892-6638

ISBN

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Numero di citazioni Wos

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Numero di citazioni Scopus

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Settori ERC

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Codici ASJC

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