title: Prostaglandin D₂ induces contractions through activation of TP receptors in peripheral lung tissue from the guinea pig.
abstract: Prostaglandin D(2) (PGD(2)), released through mast cell activation, is used as a non-invasive biomarker in patients with asthma. Since PGD(2) can elicit opposing effects on airway tone via activation of the PGD(2) receptors DP(1) and DP(2) as well as the thromboxane receptor TP, the aim of this study was to characterize the receptors that are activated by PGD(2) in the guinea pig lung parenchyma. PGD(2) and the thromboxane analog U46619 induced concentration-dependent contractions. U46619 was more potent and caused stronger effect than PGD(2). The specific TP receptor antagonist SQ-29548 and the combined TP and DP(2) receptor antagonist BAYu3405 concentration-dependently shifted the curves for both agonists to the right. The DP(1) receptor agonist BW245 induced a weak relaxation at high concentrations, whereas the DP(1) receptor antagonist BWA868C did not affect the PGD(2) induced contractions. The specific DP(2) receptor agonist 13,14-dihydro-15-keto-PGD(2) 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 PGD(2) and U46619. When the lung parenchyma from ovalbumin sensitized guinea pigs were exposed to ovalbumin, both thromboxane B(2) and PGD(2) were released. Ovalbumin also induced maximal contractions at similar level as PGD(2) in the parenchyma, which was partly reduced by SQ-29548. These data show that PGD(2) 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.
authors.affiliation: Experimental Asthma and Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden. Anna-Karin.Larsson@med.lu.se
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Larsson
authors.forename: Annika
authors.initials: A
authors.lastname: Hagfjärd
authors.forename: Sven-Erik
authors.initials: SE
authors.lastname: Dahlén
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010047:Ovalbumin / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D017482:Receptors, Thromboxane / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000941:Antigens; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D010047:Ovalbumin; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor