Role of NAADP for Calcium Signaling in the Salivary Gland

Abstract

The secretion of saliva in response to physiological demand is under control of the autonomic nervous system. Coordination and regulation of intracellular Ca2+ signaling following autonomic activation is crucial for proper salivary secretion. Previous work from our lab has demonstrated parotid acinar cells contain an abundant and polarized distribution of acidic organelles. Furthermore, acidic organelles are recruited for agonist-induced Ca2+ signaling following cAMP elevation. The current study interrogated a role for NAADP, a potent second messenger known to release Ca2+ from acidic organelles. In parotid acinar cells, initial results demonstrated NED19, an inherently fluorescent NAADP receptor inhibitor, was localized to acidic endosomes. Additionally, using a whole-cell patch clamp method to dialyze NAADP into parotid acini resulted in robust Ca2+ -activated Cl-currents. Peak activation occurred at low nanomolar concentrations of NAADP and higher concentrations showed an inhibitory effect. These observations suggest a role for NAADP in producing the fluid component of saliva. Thus, this work identifies a NAADP signaling pathway as a potential therapeutic target for people suffering from salivary hypofunction.