TRPV1 as a cough sensor and its temperature-sensitive properties.

In the respiratory tract, TRPV1, a non-selective cation channel and a polymodal transducer, is expressed primarily in non-myelinated sensory nerves. A significant role of TRPV1 in eliciting the cough reflex has been extensively documented. Inhalation of capsaicin aerosol, a selective agonist of TRPV1, consistently and reproducibly evoked coughs in a dose-dependent manner in both healthy humans and in patients with airway inflammatory diseases. A number of endogenous inflammatory mediators known to upregulate the TRPV1 sensitivity, such as prostaglandin E(2) and bradykinin, also enhanced the cough sensitivity. Furthermore, a substantial increase of TRPV1-immunoreactive nerve profiles was found in the bronchial tissue of patients with chronic cough. In addition to the cough reflex, activation of TRPV1-expressing sensory nerves in the airways is also known to elicit reflex bronchoconstriction and mucus secretion mediated through cholinergic pathways. One of the physiological stimuli known to activate TRPV1 receptor directly is high temperature. Recent studies have demonstrated that increasing temperature within the normal physiological range significantly elevated the baseline activity and sensitivity of isolated rat vagal pulmonary sensory neurons, and the sensitizing effect of hyperthermia appeared to be mediated selectively through the TRPV1 channel. This temperature-sensitive property of TRPV1 may play an important role in regulating the physiological function of the TRPV1-expressing airway sensory nerves and the sensitivity of their reflex responses, such as cough and reflex bronchoconstriction.