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.

NAADP-induced Ca(2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae / Gambara, G; Billington, Ra; Debidda, M; D'Alessio, A; Palombi, F; Ziparo, E; Genazzani, Aa; Filippini, A.. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 216:(2008), pp. 396-404. [10.1002/jcp.21407]

NAADP-induced Ca(2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae.

GAMBARA, Guido;PALOMBI, Fioretta;ZIPARO, Elio;FILIPPINI, Antonio
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.
2008
01 Pubblicazione su rivista::01a Articolo in rivista
NAADP-induced Ca(2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae / Gambara, G; Billington, Ra; Debidda, M; D'Alessio, A; Palombi, F; Ziparo, E; Genazzani, Aa; Filippini, A.. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 216:(2008), pp. 396-404. [10.1002/jcp.21407]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1033285
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