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A transport mechanism for NAADP in a rat basophilic cell line
Author(s) -
Billington R. A.,
Bellomo E. A.,
Floriddia E. M.,
Erriquez J.,
Distasi C.,
Genazzani A. A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-5058fje
Subject(s) - intracellular , extracellular , autocrine signalling , paracrine signalling , second messenger system , microbiology and biotechnology , cell culture , chemistry , biochemistry , biology , biophysics , receptor , genetics
NAADP is a second messenger that releases Ca 2+ from intracellular stores. Surprisingly, it has been recently shown that extracellular application of NAADP is capable of inducing intracellular Ca 2+ release. This is particularly important since the only mammalian enzymes known to catalyze the synthesis of this second messenger are located extracellularly. In the present manuscript, we have investigated whether mammalian cells possess a transport system capable of transporting this highly charged molecule into cells. Indeed, in RBL‐2H3 cells, a rat basophilic cell line, and in SK‐N‐BE cells, a neuroblastoma cell line, [ 32 P]NAADP is efficiently transported inside cells. NAADP transport is Na + and Ca 2+ dependent, is partially blocked by dipyridamole, but is unaffected by nitrobenzylthioinosine. RBL‐2H3 cells also transport [ 32 P]cADPR, but the differences in the pharmacological profile suggest that NAADP transport proceeds by a novel mechanism. Lastly, extracellular application of NAADP, but not NADP, induced a raise in intracellular Ca 2+ . This is the first demonstration that NAADP is transported into cells and highlights the possibility that, alongside a second messenger, NAADP might also act as an autocrine/paracrine signal.