Prostaglandin D2 induces contractions through activation of TP receptors in peripheral lung tissue from the guinea pig

Prostaglandin D2 (PGD2), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD2 can elicit opposing effects on airway tone via activation of the PGD2 receptors DP1 and DP2 as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD2 in the guinea pig lung parenchyma. PGD2 and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD2. The specific TP receptor antagonist SQ-29548 and the combined TP and DP2 receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP1 receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP1 receptor antagonist BWA868C did not affect the PGD2 induced contractions. The specific DP2 receptor agonist 13,14-dihydro-15-keto-PGD2 showed neither contractile nor relaxant effect in the parenchyma. Furthermore, studies in precision-cut lung slices specified that airways as well as pulmonary arteries and veins contracted to both PGD2 and U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were exposed to ovalbumin, both thromboxane B2 and PGD2 were released. Ovalbumin also induced maximal contractions at similar level as PGD2 in the parenchyma, which was partly reduced by SQ-29548. These data show that PGD2 should be recognized as a TP receptor agonist in the peripheral lung inducing contraction on airways, arteries and veins. Therefore, a TP receptor antagonist can be useful in combination treatment of allergic responses in asthma.