TP‐receptor activation potentiates airway stretch‐activated contractions

A deep inspiration (DI) produces a bronchodilation in healthy individuals. Conversely, in asthmatics, DIs are ineffective in producing bronchodilation, and can even cause bronchoconstriction. Interestingly, the manner by which a DI is able to cause bronchoconstriction via a stretch‐activated contraction (R stretch ) correlates positively with airway inflammation, during which there is increased production of thromboxane A 2 (TxA 2 ) and TP‐receptor activation. In this study we sought to investigate the effect of TP‐receptor activation on airway R stretch in bovine bronchial segments using the Mayflower organ bath as previously reported by our laboratory. R stretch was elicited by varying the transmural pressure under isovolumic conditions. Using a pharmacological approach, we showed a reduced R stretch response in tissues pretreated with indomethacin (Indo), a COX inhibitor; a result mimicked by the TP‐receptor antagonist ICI 192605 and by airway epithelial denudation. U46619, a TP‐receptor agonist elicited enhanced R stretch responses in a dose‐dependent manner. AH6809, an EP 1 /DP‐receptor antagonist and AL 8810, an FP‐receptor antagonist had no effect, suggesting PGE 2 , PGD 2 , and PGF 2 [alpha] are not involved in ASM R stretch . These data suggest a role for the TP‐receptor and epithelial release of TxA 2 in potentiating the effects of airway R stretch . Research Support: CIHR, NSERC