Fig. 2

Signaling pathways initiated by prostanoids released from peripheral inflammation. a PGE₂-induced activation of EP receptors in somatosensory neurons. In somatosensory neurons, the EP1 receptor is associated with the G protein, Gαq and its activation triggers the release of intracellular Ca²⁺ from the endoplasmic reticulum through inositol 1,4,5-trisphosphate (IP3) production. EP2 and EP4 receptors are coupled with Gαs, which stimulates cyclic adenosine monophosphate (cAMP) production by activating adenylyl cyclase (AC), whereas EP3 receptor-coupled Gαi activation inhibits cAMP production by inhibiting AC. cAMP in turn activates protein kinase A (PKA), causing phosphorylation of various signaling proteins including epsilon type protein kinase C (PKCε). b-d Signaling pathways initiated by the activation of DP, IP, and TP receptors in somatosensory neurons. The DP1-linked Gαs stimulates intracellular cAMP production, whereas DP2-associated Gαi inhibits cAMP production. The counter-action of DP1 and DP2 (b) receptors regulates cAMP accumulation in the cytosolic compartment. The activation of IP (c) or TP receptors (d) recruits Gαs protein, activates AC, and consequently raises the intracellular cAMP level