Figure 8.

Schematic presentation of the proposed mechanism. Extracellular β-NAD and ATP are spilled concomitantly from damaged cells. ATP binds to the ATP-sensitive P2X7 receptor of monocytic cells, induces inflammasome activation, activation of caspase-1, cleavage of pro-IL-1β and release of bioactive IL-1β. Our data suggest that β-NAD signals via P2Y receptors that activate iPLA2β and result in the production and secretion of yet unidentified bioactive mediators. These mediators seem to function as nicotinic agonists that activate non-canonical metabotropic functions at nicotinic acetylcholine receptors. Nicotinic receptor stimulation, in turn, efficiently inhibits the ion-channel function of the P2X7 receptor. It is unclear, if nicotinic receptors subunits actually form conventional pentamers as shown in the schematic drawing.