Premium
NAADP‐induced Ca 2+ signaling in response to endothelin is via the receptor subtype B and requires the integrity of lipid rafts/caveolae
Author(s) -
Gambara Guido,
Billington Richard A.,
Debidda Marcella,
D'Alessio Alessio,
Palombi Fioretta,
Ziparo Elio,
Genazzani Armando A.,
Filippini Antonio
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21407
Subject(s) - caveolae , lipid raft , endothelin receptor , signal transduction , microbiology and biotechnology , receptor , ryanodine receptor , chemistry , extracellular , biology , cell signaling , intracellular , biochemistry
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‐β‐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. J. Cell. Physiol. 216: 396–404, 2008. © 2008 Wiley‐Liss, Inc.