Figure 4. Enteric glia actively participate in purinergic neuron–glia signalling.

ADP and ATP bind to G‐protein coupled purinergic receptors P2Y1R and P2Y4R, respectively, and activate phospholipase C (PLC) and subsequent production of inositol 1,4,5‐trisphosphate (IP₃). This consequently activates IP₃ receptors (IP₃R) inducing the release of Ca²⁺ from endoplasmic reticulum (ER). Increase in the intracellular Ca²⁺ concentration [Ca²⁺]_i induces ATP release through Cx43 hemichannels. Sarco/endoplasmic reticulum Ca²⁺‐ATPase (SERCA) pumps Ca²⁺ ions back into the ER. Based from original research on enteric glial cells (Kimball & Mulholland 1996; Zhang et al. 2003; McClain et al. 2014). Not drawn to scale.