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Prostaglandin D2 inhibits mediator release and antigen induced bronchoconstriction in the Guinea pig trachea by activation of DP1 receptors.
Säfholm, Jesper; Abma, Willem; Liu, Jielu; Balgoma, David; Fauland, Alexander; Kolmert, Johan; Wheelock, Craig E; Adner, Mikael; Dahlén, Sven-Erik.
Afiliación
  • Säfholm J; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden. Electronic address: jesper.safholm@ki.se.
  • Abma W; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
  • Liu J; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
  • Balgoma D; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Fauland A; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Kolmert J; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Wheelock CE; Division of Physiological Chemistry II, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Adner M; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
  • Dahlén SE; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Eur J Pharmacol ; 907: 174282, 2021 Sep 15.
Article en En | MEDLINE | ID: mdl-34175307
The mechanism by which cyclooxygenase (COX) inhibition increases antigen-induced responses in airways remains unknown. Male albino guinea pigs were sensitized to ovalbumin (OVA). Intact rings of the trachea were isolated and mounted in organ baths for either force measurements or lipid mediator release analysis by UPLC-MS/MS or EIA following relevant pharmacological interventions. First, challenge with OVA increased the release of all primary prostanoids (prostaglandin (PG) D2/E2/F2α/I2 and thromboxanes). This release was eliminated by unselective COX inhibition (indomethacin) whereas selective inhibition of COX-2 (lumiracoxib) did not inhibit release of PGD2 or thromboxanes. Additionally, the increased levels of leukotriene B4 and E4 after OVA were further amplified by unselective COX inhibition. Second, unselective inhibition of COX and selective inhibition of the prostaglandin D synthase (2-Phenyl-Pyrimidine-5-Carboxylic Acid (2,3-dihydro-indol-1-yl)-amide) amplified the antigen-induced bronchoconstriction which was reversed by exogenous PGD2. Third, a DP1 receptor agonist (BW 245c) concentration-dependently reduced the antigen-induced constriction as well as reducing released histamine and cysteinyl-leukotrienes, a response inhibited by the DP1 receptor antagonist (MK-524). In contrast, a DP2 receptor agonist (15(R)-15-methyl PGD2) failed to modulate the OVA-induced constriction. In the guinea pig trachea, endogenous PGD2 is generated via COX-1 and mediates an inhibitory effect of the antigen-induced bronchoconstriction via DP1 receptors inhibiting mast cell release of bronchoconstrictive mediators. Removal of this protective function by COX-inhibition results in increased release of mast cell mediators and enhanced bronchoconstriction.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tráquea / Leucotrienos / Cisteína Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tráquea / Leucotrienos / Cisteína Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2021 Tipo del documento: Article Pais de publicación: Países Bajos