Function and signal transduction pathway of TRPM8 in LUT. TRPM8 is widely distributed in the LUT, lungs, as well as the nervous system. Calcium ions can influx into the cell after the channel is activated, and phosphoinositides (PIP2) can be back hydrolyzed to soluble inositol 1,4,5-trisphosphate (IP3) and membrane-bound diacylglycerol (DAG) under the action of calcium-sensitive phospholipase (PLC) and IP3 secretion, which in turn can affect the concentration of calcium ions and thus activate the TRPM8 pathway. Channel activation is also impeded by cold or other chemical factors.