Investigating the role of prostaglandin D ₂ in airway sensory nerve firing: Relevance to disease

Levels of Prostaglandin D 2 (PGD 2 ) are known to be increased in the lungs of patients with respiratory diseases such as asthma and COPD. Indeed, there is intense ongoing research into the inflammatory role of PGD 2 and the role of CRTH2 (one of two PGD 2 receptors). However, there is little known about the function of PGD 2 on airway sensory nerves and cough in these diseases. As excessive coughing is a key symptom of these diseases, the aim of this study is to determine how PGD 2 , and the two receptors it acts on, impact on airway sensory nerves. Initial studies showed that inhaled PGD 2 caused dose-related coughing in guinea pigs (GP). PGD 2 increased the calcium signal in primary GP airway ganglia cells and RT-PCR showed both receptors for PGD 2 (DP 1 and CRTH2) are expressed. Using pharmacological tools and tissues harvested from human lungs and PGD 2 receptor deficient mice, we generated data that showed that PGD 2 activates sensory nerves via the DP 1 receptor. This was further corroborated in an in vivo single fibre recording preparation. As we could detect CRTH2 expression in the nerve ganglia, we went on to study whether receptor activation modulated responses to other tussive agents. Interestingly, the data showed that activating CRTH2 inhibited capsaicin (TRPV1 agonist) induced sensory nerve firing in vitro and in vivo . In conclusion, PGD 2 can activate airway sensory nerves via the DP 1 receptor and appears to attenuate TRPV1 driven nerve firing via the CRTH2 receptor. This data suggests that the excessive cough observed in respiratory diseases could be due to the higher levels of PGD 2 .