Prostaglandin D 2 and the role of the DP 1 , DP 2 and TP receptors in the control of airway reflex events

• Published in: The European respiratory journal Vol. 45; no. 4; pp. 1108 - 1118
• Main Authors: Maher, Sarah A., Birrell, Mark A., Adcock, John J., Wortley, Michael A., Dubuis, Eric D., Bonvini, Sara J., Grace, Megan S., Belvisi, Maria G.
• Format: Journal Article
• Language: English
• Published: 01.04.2015
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/09031936.00061614

Prostaglandin D 2 (PGD 2 ) causes cough and levels are increased in asthma suggesting that it may contribute to symptoms. Although the prostaglandin D 2 receptor 2 (DP 2 ) is a target for numerous drug discovery programmes little is known about the actions of PGD 2 on sensory nerves and cough. We used human and guinea pig bioassays, in vivo electrophysiology and a guinea pig conscious cough model to assess the effect of prostaglandin D 2 receptor (DP 1 ), DP 2 and thromboxane receptor antagonism on PGD 2 responses. PGD 2 caused cough in a conscious guinea pig model and an increase in calcium in airway jugular ganglia. Using pharmacology and receptor-deficient mice we showed that the DP 1 receptor mediates sensory nerve activation in mouse, guinea pig and human vagal afferents. In vivo , PGD 2 and a DP 1 receptor agonist, but not a DP 2 receptor agonist, activated single airway C-fibres. Interestingly, activation of DP 2 inhibited sensory nerve firing to capsaicin in vitro and in vivo . The DP 1 receptor could be a therapeutic target for symptoms associated with asthma. Where endogenous PGD 2 levels are elevated, loss of DP 2 receptor-mediated inhibition of sensory nerves may lead to an increase in vagally associated symptoms and the potential for such adverse effects should be investigated in clinical studies with DP 2 antagonists.