Figure 1.

Identified signaling pathways involved in TRPM8 channel regulation. 1 – Activation of PLCδ4 by calcium influx leads to PIP2 depletion and inhibition of TRPM8; 2 – Gq-coupled receptor-mediated stimulation of PLCβ leads to PIP2 depletion and inhibition of TRPM8. 3 – In response to the stimulation of the bradykinin receptor (B2R), Gαq directly binds to and inhibit TRPM8; 4 – DAG and calcium influx mediate the activation of PKC, which contributes to a Ca2+ mediated desensitization of TRPM8; 5 – Activation of Gs-coupled receptors leads to a PKA-mediated inhibition of TRPM8; 6 – Testosterone activates TRPM8 directly or indirectly through the AR signaling pathway that involves Src, ERK and MAPK. Abbreviations: AR-androgen receptor, DAG – diacylglycerol, ERK – extracellular signal-regulated kinase, GPCR – G protein-coupled receptor, IP3 – inositol trisphosphate, MAPK – mitogen-activated protein kinase, PIP2 – phosphatidylinositol bisphosphate, PKA – protein kinase A, PKC – protein kinase C, PLC-phospholipase C