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

Alessio D'Alessio, G Gambara, Ra Billington, M Debidda, F Palombi, E Ziparo, Aa Genazzani, A. Filippini

Risultato della ricerca: Contributo in rivistaArticolo in rivista

30 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)396-404
Numero di pagine9
RivistaJournal of Cellular Physiology
Volume216
DOI
Stato di pubblicazionePubblicato - 2008

Keywords

  • Antigens, CD38
  • Calcium
  • Calcium Signaling
  • Caveolin 1
  • Endothelin-1
  • Endothelins
  • Enzyme Inhibitors
  • Myocytes, Smooth Muscle
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Seminiferous Tubules
  • beta-Cyclodextrins

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