Current asthma therapy may not adequately target contraction of smaller intrapulmonary airways, which are a major site of airway obstruction and inflammation. The aim of this study was to characterise responses of mouse intrapulmonary airways to prostaglandin E₂ (PGE₂) and compare its dilator efficacy with the β₂-adrenoceptor agonist salbutamol in situ, using lung slices.

Lung slices (150 μm) were prepared from male Balb/C mice. Changes in intrapulmonary airway lumen area were recorded and analysed by phase-contrast microscopy. Relaxation to PGE₂ and salbutamol were assessed following various levels of pre-contraction with methacholine, serotonin or endothelin-1, as well as following overnight incubation with PGE₂ or salbutamol. The mechanism of PGE₂-mediated relaxation was explored using selective EP antagonists (EP_1/2 AH6809; EP₄ L-161982) and Ca²⁺-permeabilized slices, where airway responses are due to regulation of Ca²⁺-sensitivity alone.

PGE₂ elicited EP_1/2-mediated relaxation of intrapulmonary airways. PGE₂ was more potent than salbutamol in opposing submaximal pre-contraction to all constrictors tested, and only PGE₂ opposed maximal pre-contraction with endothelin-1. Relaxation to PGE₂ was maintained when contraction to methacholine was mediated via increased Ca²⁺-sensitivity alone. PGE₂ was less sensitive to homologous or heterologous desensitization of its receptors than salbutamol.

The greater efficacy and potency of PGE₂ compared to salbutamol in mouse intrapulmonary airways supports further investigation of the mechanisms underlying this improved dilator responsiveness for the treatment of severe asthma.