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 dinucleotide phosphate (NAADP(+)) dose-dependently stimulated intracellular Ca2+-signaling. At a concentration of 10 nM NAADP(+) evoked repetitive and long-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+-oscillations was observed. Higher concentrations of NAADP(+) (1 and 10 mu M) gradually reduced the initial Ca2+-peak, and a complete self-inactivation of Ca2+-signals was seen at 100 mu M. 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 Ca2+-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 Ca2+-signaling via the T cell receptor/CD3 complex, indicating that a functional NAADP(+) Ca2+-release system is essential for T-lymphocyte Ca2+-signaling.