Figure 2.

Proposed purinergic signaling pathways underlying the cellular responses associated with P2 receptor activation in various areas of the tooth. The involvement of purinergic receptors in cytokine expression and secretion has been examined in dental pulp cells (P2Y₆-mediated IL-6 release), in gingival fibroblasts (P2X₇-mediated IL-8 release), and in gingival epithelial cells (inflammasome activation via ATP-ligation of P2X₇R and caspase-1 cleavage of pro-IL-1β). In addition, hemichannels have been identified as a potential conduit for ATP release from periodontal ligament cells, with stimulation of P2Y₁R leading to up-regulation of osteopontin and receptor activator of nuclear factor kappa B ligand (RANKL). Homomeric P2X₃ receptors and/or heteromeric P2X₂/P2X₃ receptors on nerve terminals in the dental pulp transmit nociceptive signals upon stimulation by ATP released from numerous neighboring sources.