title: Chemosensory TRP channels in the respiratory tract: role in toxic lung injury and potential as "sweet spots" for targeted therapies.
abstract: Acute toxic lung injury by reactive inhalational compounds is an important and still unresolved medical problem. Hazardous gases or vapors, e. g. chlorine, phosgene, sulfur mustard or methyl isocyanate, are released during occupational accidents or combustion processes and also represent a potential threat in terroristic scenarios. According to their broad-range chemical reactivity, the mechanism of lung injury evoked by these agents has long been described as rather unspecific. Consequently, therapeutic options are still restricted to symptomatic treatment. However, in recent years, ion channels of the transient receptor potential (TRP) family have been identified to act as specific sensor molecules expressed in the respiratory tract and to engage defined signaling pathways upon inhalational exposure to toxic challenges. These pulmonary receptor molecules have been primarily characterized in sensory neurons of the lung. However, chemosensory molecules are also expressed in non-neuronal cells, e.g. in the lung epithelium as well as in the pulmonary vasculature. Thus, activation of respiratory chemosensors by toxic inhalants promotes a complex signaling network directly or indirectly regulating pulmonary blood flow, the integrity of the epithelial lining, and the mucociliary clearance of the bronchial system. This review gives a synopsis on reactive lung-toxic agents and their specific target molecules in the lung and summarizes the current knowledge about the pathophysiological role of chemosensory signaling in neuronal and non-neuronal cells in toxic lung injury. Finally, we describe possible future strategies for a causal, specifically tailored treatment option based on the mechanistic understanding of molecular events ensuing inhalation of lung-toxic agents.
authors.affiliation: Rudolf Boehm-Institut für Pharmakologie und Toxikologie, Selbständige Abteilung für Klinische Pharmakologie, Universität Leipzig, Härtelstr. 16-18, Leipzig, 04107, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Büch
authors.forename: Eva
authors.initials: E
authors.lastname: Schäfer
authors.forename: Dirk
authors.initials: D
authors.lastname: Steinritz
authors.forename: Alexander
authors.initials: A
authors.lastname: Dietrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
mesh_terms: D000818:Animals; D003371:Cough / Q000503:physiopathology; D006801:Humans; D007509:Irritants / Q000633:toxicity; D055370:Lung Injury / Q000139:chemically induced* / Q000628:therapy; D009079:Mucociliary Clearance; D050051:Transient Receptor Potential Channels / Q000737:chemistry / Q000502:physiology*
chemical_list: D007509:Irritants; D050051:Transient Receptor Potential Channels