We have investigated the role of NAADP-mediated Ca(2+) mobilization in endothelin (ET) signaling via endothelin receptor subtype A (ETA) and endothelin receptor subtype B (ETB) in rat peritubular smooth muscle cells. Microinjection and extracellular application of NAADP were both able to elicit Ca(2+) release which was blocked by inhibitory concentrations of NAADP, by impairing Ca(2+) uptake in acidic stores with bafilomycin, and by thapsigargin. Ca(2+) release in response to selective ETB stimulation was abolished by inhibition of NAADP signaling through the same strategies, while these treatments only partially impaired ETA-dependent Ca(2+) signaling, showing that transduction of the ETB signal is dependent on NAADP. In addition, we show that lipid rafts/caveolae contain ETA, ETB, and NAADP/cADPR generating enzyme CD38 and that stimulation of ETB receptors results in increased CD38 activity; interestingly, ETB- (but not ETA-) mediated Ca(2+) responses were antagonized by disruption of lipid rafts/caveolae with methyl-beta-cyclodextrin. These data demonstrate a primary role of NAADP in ETB-mediated Ca(2+) signaling and strongly suggest a novel role of lipid rafts/caveolae in triggering ET-induced NAADP signaling.

Gambara, G., Billington, R., Debidda, M., D'alessio, A., Palombi, F., Ziparo, E., Genazzani, A., Filippini, A., NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae, <<JOURNAL OF CELLULAR PHYSIOLOGY>>, 2008; 216 (2): 396-404. [doi:10.1002/jcp.21407] [http://hdl.handle.net/10807/13529]

NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae

D'Alessio, Alessio;
2008

Abstract

We have investigated the role of NAADP-mediated Ca(2+) mobilization in endothelin (ET) signaling via endothelin receptor subtype A (ETA) and endothelin receptor subtype B (ETB) in rat peritubular smooth muscle cells. Microinjection and extracellular application of NAADP were both able to elicit Ca(2+) release which was blocked by inhibitory concentrations of NAADP, by impairing Ca(2+) uptake in acidic stores with bafilomycin, and by thapsigargin. Ca(2+) release in response to selective ETB stimulation was abolished by inhibition of NAADP signaling through the same strategies, while these treatments only partially impaired ETA-dependent Ca(2+) signaling, showing that transduction of the ETB signal is dependent on NAADP. In addition, we show that lipid rafts/caveolae contain ETA, ETB, and NAADP/cADPR generating enzyme CD38 and that stimulation of ETB receptors results in increased CD38 activity; interestingly, ETB- (but not ETA-) mediated Ca(2+) responses were antagonized by disruption of lipid rafts/caveolae with methyl-beta-cyclodextrin. These data demonstrate a primary role of NAADP in ETB-mediated Ca(2+) signaling and strongly suggest a novel role of lipid rafts/caveolae in triggering ET-induced NAADP signaling.
Inglese
Gambara, G., Billington, R., Debidda, M., D'alessio, A., Palombi, F., Ziparo, E., Genazzani, A., Filippini, A., NAADP-induced Ca2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae, <<JOURNAL OF CELLULAR PHYSIOLOGY>>, 2008; 216 (2): 396-404. [doi:10.1002/jcp.21407] [http://hdl.handle.net/10807/13529]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/13529
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