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 μM) gradually reduced the initial Ca²⁺-peak, and a complete self-inactivation of Ca²⁺-signals was seen at 100 μM. 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.