Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential regulator of T-lymphocyte Ca2+-signaling

Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine di nucleotide phosphate (NAADP(+)) dose-dependently stimulated intracellular C a2+-signaling. At a concentration of 10 nM NAADP(+) evoked repetitive and l ong-lasting Ca2+ oscillations of low amplitude, whereas at 50 and 100 nM, a rapid and high initial Ca2+-peak followed by trains of smaller Ca2+-oscill ations was observed. Higher concentrations of NAADP(+) (1 and 10 mu M) grad ually reduced the initial Ca2+-peak, and a complete self-inactivation of Ca 2+-signals was seen at 100 mu M. The effect of NAADP(+) was specific as it was not observed with nicotinamide adenine dinucleotide phosphate. Both ino sitol 1,4,5-trisphosphate- and cyclic adenosine diphosphoribose-mediated Ca 2+-signaling were efficiently inhibited by coinjection of a self-inactivati ng concentration of NAADP(+), Most importantly, microinjection of a self-in activating concentration of NAADP(+) completely abolished subsequent stimul ation of Ca2+-signaling via the T cell receptor/CD3 complex, indicating tha t a functional NAADP(+) Ca2+-release system is essential for T-lymphocyte C a2+-signaling.