Figure 2.

Summary of distinct modulation of TRPV1 and TRPM8 by inflammatory mediators activating Gq coupled receptors. The inflammatory mediator BK sensitizes hyperalgesia-mediated TRPV1, but inhibits analgesia-mediated TRPM8, resulting in inflammatory hyperalgesia. The sensitization of TRPV1 is caused by the phosphorylation of TRPV1 at S502/S801 (not depicted) by PKCε, which is anchored adjacent to TRPV1 by the scaffolding protein AKAP79/150 forming a macro-signaling complex. However, the inhibition of TRPM8 is mediated by a direct action of activated Gq on TRPM8 independently of the PLC signaling. Note that the basal thermal sensitivity of TRPV1 is determined by the basal phosphorylation of TRPV1 at T705 by PKCβII, which binds to TRPV1 forming another local protein complex with TRPV1.