In vitro-induced human airway hyperresponsiveness to bradykinin.
Lipopolysaccharide (LPS) and interleukin (IL)-1beta have been reported to induce airway hyperresponsiveness in several animal models. This study investigated the effect of LPS or IL-1beta on bradykinin-induced human isolated bronchi contraction. LPS (100 ng x mL(-1) for 3-6 h) and IL-1beta (3x10(-10) and 3x10(-9) M for 20 min to 3 h) time-dependently potentiated bradykinin-induced contraction. This contraction was abolished, as in control experiments, by indomethacin (10(-6) M) or by the thromboxane (Tx) receptor antagonist GR 32191 but not by the cyclo-oxygenase-2 inhibitor, CGP28238. In contrast, the Tx mimetic U46619-induced contraction of human bronchi was not enhanced IL-1beta pretreatment. In the presence of GR 32191 (10(-6) M), bradykinin induced a prostanoid dependent relaxation that was not significantly modified by IL-1beta pretreatment. Determination of prostanoids in the organ bath fluid showed that bradykinin induced TxB2, the stable metabolite of TxA2, and 6-keto prostaglandin F1alpha, the stable metabolite of PGI2, release. Only TxA2 release was potentiated by IL-1beta. Taken together our results suggest that interleukin-1beta (1-3 h)-induced potentiation of the effect of bradykinin is linked to an increased activity of thromboxane synthase and, in turn, to increased thromboxane synthesis.
Molimard
M
M
Dépt de Pharmacologie, Université Victor Segalen Bordeaux II, France.
Naline
E
E
Boichot
E
E
Devillier
P
P
Lagente
V
V
Bégaud
B
B
Advenier
C
C
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000368:Aged; D001713:Biphenyl Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology* / Q000502:physiology; D001980:Bronchi / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008875:Middle Aged; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013931:Thromboxanes / Q000378:metabolism
D001713:Biphenyl Compounds; D016861:Cyclooxygenase Inhibitors; D006538:Heptanoic Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D017482:Receptors, Thromboxane; D013931:Thromboxanes; D015121:6-Ketoprostaglandin F1 alpha; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C060013:vapiprost; D001920:Bradykinin; D007213:Indomethacin