Inhaled Volatile Molecules-Responsive TRP Channels as Non-Olfactory Receptors

Abstract

Generally, odorant molecules are detected by olfactory receptors, which are specialized chemoreceptors expressed in olfactory neurons. Besides odorant molecules, certain volatile molecules can be inhaled through the respiratory tract, often leading to pathophysiological changes in the body. These inhaled molecules mediate cellular signaling through the activation of the Ca²⁺-permeable transient receptor potential (TRP) channels in peripheral tissues. This review provides a comprehensive overview of TRP channels that are involved in the detection and response to volatile molecules, including hazardous substances, anesthetics, plant-derived compounds, and pheromones. The review aims to shed light on the biological mechanisms underlying the sensing of inhaled volatile molecules. Therefore, this review will contribute to a better understanding of the roles of TRP channels in the response to inhaled molecules, providing insights into their implications for human health and disease.

Keywords: Non-olfactory receptors; TRPA1; TRPV1; Transient receptor potential channel; Volatile organic compound.

Fig. 1

A schematic overview of the inhaled volatile compounds and the TRP channels that respond within the body.

Fig. 2

An overview of the types of molecules that elicit activation of TRP channels and the associated symptoms.

Fig. 3

The pheromone sensing mechanism by the TRPC2 channel. In the vomeronasal organ, the pheromone signal transduction pathway begins at vomeronasal receptors. Upon pheromones binding, the V1R/V2R activates G-proteins. The activated G-proteins stimulate the cleavage of PIP2 into IP3 and DAG via PLC. DAG activates TRPC2 channel, leading to influx of cationic ions. Ca²⁺/calmodulin directly inhibits the activity of TRPC2. The human TRPC2 gene is a pseudogene that generates premature stop codons, resulting in a severely truncated protein. DAG, diacylglycerol; GDP, guanosine diphosphate; GTP, guanosine triphosphate; Ins(1,4,5)P3, inositol 1,4,5-trisphosphate; PIP, phosphatidylinositol-4,5-bisphosphate; PLC, phospholipase C; CaM, calmodulin.