Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential regulator of T-lymphocyte Ca(2+)-signaling.
Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine dinucleotide phosphate (NAADP(+)) dose-dependently stimulated intracellular Ca(2+)-signaling. At a concentration of 10 nM NAADP(+) evoked repetitive and long-lasting Ca(2+)-oscillations of low amplitude, whereas at 50 and 100 nM, a rapid and high initial Ca(2+)-peak followed by trains of smaller Ca(2+)-oscillations was observed. Higher concentrations of NAADP(+) (1 and 10 microM) gradually reduced the initial Ca(2+)-peak, and a complete self-inactivation of Ca(2+)-signals was seen at 100 microM. The effect of NAADP(+) was specific as it was not observed with nicotinamide adenine dinucleotide phosphate. Both inositol 1,4, 5-trisphosphate- and cyclic adenosine diphosphoribose-mediated Ca(2+)-signaling were efficiently inhibited by coinjection of a self-inactivating concentration of NAADP(+). Most importantly, microinjection of a self-inactivating concentration of NAADP(+) completely abolished subsequent stimulation of Ca(2+)-signaling via the T cell receptor/CD3 complex, indicating that a functional NAADP(+) Ca(2+)-release system is essential for T-lymphocyte Ca(2+)-signaling.
Institute of Medical Biochemistry and Molecular Biology, Division of Cellular Signal Transduction, University of Hamburg, D-20146 Hamburg, Germany.
I
I
Berg
B V
BV
Potter
G W
GW
Mayr
A H
AH
Guse
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D020013:Calcium Signaling; D036563:Cyclic ADP-Ribose; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D008845:Microinjections; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate