Abstract
Transient receptor potential (TRP) cation channels are a functionally diverse family of proteins. While thorough elucidation of the seemingly endless biological functions that can potentially be performed by, or at least effected by, TRP channels is far from a reality, accumulating experimental evidence for some TRP channels demonstrates vital contributions of select TRP channels to a number of critical physiological functions in select organ systems and cell types. In the respiratory tract, TRP channel expression is highly variable, depending upon anatomical location (i.e., nasal, tracheal, bronchiole/bronchiolar, terminal/alveolar) and cell type (i.e., neuronal, epithelial, endothelial, resident immune, etc.), with high abundance of TRP channels in sensory neurons and some epithelial and endothelial cell types. The focus of this chapter is on TRP channels in the lung and mechanisms by which select TRP channels contribute to reflex responses, pulmonary inflammation, and injury commonly associated with exposure to a variety of exogenous and endogenous pneumotoxic agents. Both neurogenic (classical) and nonneurogenic (novel) mechanisms by which TRP channels influence respiratory physiology and pulmonary homeostasis will be covered since recent evidence strongly suggests that TRP channels expressed by nonneuronal cells may play equally vital roles in mounting and controlling various phases of inflammatory responses and injury associated with certain stimuli. The chapter reviews basic immunology and how select components of the immune response act in concert in the respiratory tract, the expression and basic pharmacology of TRP channels, mechanisms by which different TRP channels regulate select components of innate immunity, and specific examples of TRP channel-mediated pneumotoxicity elicited by xenobiotics and a variety of endogenous proinflammatory agents.
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