Figure 8.

Proposed model of the mechanisms involved in glial cell-driven enteric neuron death during acute inflammation. The activation of neuronal P2X7 receptors (P2X7Rs) leads to adenosine triphosphate (ATP) release through pannexin-1 (panx1) channels that recruits activity in the surrounding glia by activating glial P2Y1 receptors (P2Y1Rs). Intracellular signaling pathways downstream of P2Y1R activation drive glial inducible nitric oxide synthase (iNOS) production and glial NO potentiates connexin-43 (Cx43) hemichannel-dependent ATP release. Glial NO may also feed back on neurons to block panx1 channel activity. Large quantities of ATP are released through glial Cx43 and act on neuronal P2X7Rs to drive neuron death.