ABSTRACT
Disclaimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
8.1.1 Vanilloid Receptors and Respiratory Toxicology . . . . . . . 298 8.1.2 Historical Perspective on Capsaicinoids . . . . . . . . . . . . . 299 8.1.3 Identification and Cloning of TRPV1 . . . . . . . . . . . . . . . 301 8.1.4 Newly Discovered Members of the TRP
Superfamily of Ion Channels . . . . . . . . . . . . . . . . . . . . . 303 8.1.5 Functional Characteristics of TRPV1 and Other
Mammalian TRP Channels . . . . . . . . . . . . . . . . . . . . . . . 305 8.1.6 Homogenous and Heterogeneous Multisubunit
TRP Complexes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 8.1.7 Chemical and Thermal Nociception by
TRP Channels . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311 8.2 Expression of Vanilloid Receptors
in the Respiratory Tract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 313 8.2.1 Identification of TRPV1 Expression in Sensory
Neurons and Epithelial Cells by Radiolabeled Ligand-Binding and Hybridization Assays . . . . . . . . . . . . 313
8.3 Activation of TRP/Vanilloid Receptors in Respiratory Tissues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315 8.3.1 The Cough Reflex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
8.3.2 Neurogenic Inflammation . . . . . . . . . . . . . . . . . . . . . . . . 316 8.3.3 Role of TRPV1 in Pepper Spray Toxicity . . . . . . . . . . . . 318 8.3.4 TRPV1-Mediated Responses to Ambient
Particulate Material. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325 8.4 Role of Vanilloid Receptors in Human
Respiratory Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329 8.4.1 Are Vanilloid Receptors Important in
Airway Hypersensitivity Disorders? . . . . . . . . . . . . . . . . . 329 8.4.2 Do Other Vanilloid Receptors Modulate Cellular
Responses to Respiratory Irritants and Toxicants? . . . . . . 331 8.4.3 Can Vanilloid Receptor Ligands Be Used
Therapeutically? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 8.5 Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336 8.6 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
This document has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, or does mention of trade names or commercial products constitute the endorsement or recommendation for use.
