Role of TRPV receptors in respiratory diseases

Transient receptor potential vanilloid type channels (TRPVs) are expressed in several cell types in human and animal lungs. Increasing evidence has demonstrated important roles of these cation channels, particularly TRPV1 and TRPV4, in the regulation of airway function. These TRPVs can be activated by a number of endogenous substances (hydrogen ion, certain lipoxygenase products, etc.) and changes in physiological conditions (e.g., temperature, osmolarity, etc.). Activation of these channels can evoke Ca²⁺ influx and excitation of the neuron. TRPV1 channels are generally expressed in non-myelinated afferents innervating the airways and lungs, which also contain sensory neuropeptides such as tachykinins. Upon stimulation, these sensory nerves elicit centrally-mediated reflex responses as well as local release of tachykinins, and result in cough, airway irritation, reflex bronchoconstriction and neurogenic inflammation in the airways. Recent studies clearly demonstrated that the excitability of TRPV1 channels is up-regulated by certain autacoids (e.g., prostaglandin E₂, bradykinin) released during airway inflammatory reaction. Under these conditions, the TRPV1 can be activated by a slight increase in airway temperature or tissue acidity. Indirect evidence also suggests that TRPV channels may play a part in the pathogenesis of certain respiratory diseases such as asthma and chronic cough. Therefore, the potential use of TRPV antagonists as a novel therapy for these diseases certainly merits further investigation.