Possible role of thromboxane A2 in hyperresponsiveness of isolated rat lung tissue in a Sephadex-induced eosinophilia model.
Antigen-stimulated contraction and release of chemical mediators were examined in saline- or Sephadex-treated rat lung parenchymal strips. Sephadex treatment caused eosinophilia in the blood and the lung tissue. Antigen challenge of the isolated parenchymal strips in Sephadex-treated rat was followed by passive sensitization, resulted in an augmented contraction and elevated releases of thromboxane (TX) B2 and peptide-leukotrienes (p-LTs) in bath fluid compared with those of saline-treated control. Although 5-hydroxytryptamine (5-HT) and histamine were significantly released after antigen challenge, the levels were not different between saline- and Sephadex-treated groups. DP-1904, a selective thromboxane synthetase inhibitor, and methysergide but not atropine significantly reduced the augmented contraction and inhibited the elevated TXB2 release in the Sephadex-treated group. Similar increased contraction and the elevated TXB2 release above were observed when Sephadex-treated rat lung strips were stimulated by exogenous 5-HT and LTD4. These augmented contractions were closely correlated with the increase in TXB2 level (r = 0.83; p < 0.01). In addition, contraction to U-46619, a thromboxane mimetic, was significantly greater in Sephadex-treated rat lung strips. Our results indicate that the ability of Sephadex-treated rat lung tissue to synthesize newly generated mediators such as TXA2 and p-LTs is increased, and the spasmogenic susceptibility of the lung tissue to TXA2 itself is modified by Sephadex treatment, suggesting these are due to the augmented contraction in an established hyperresponsiveness state induced by Sephadex.
Takami
M
M
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Tokyo, Japan.
Matsumoto
K
K
Takata
Y
Y
Furuhama
K
K
Tsukada
W
W
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000503:physiopathology*; D003911:Dextrans / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D017998:Leukotriene D4 / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011657:Pulmonary Eosinophilia / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D003911:Dextrans; D007093:Imidazoles; D011450:Prostaglandin Endoperoxides, Synthetic; D013764:Tetrahydronaphthalenes; D014662:Vasoconstrictor Agents; D013928:Thromboxane A2; D017998:Leukotriene D4; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001285:Atropine; C025614:sephadex; C056295:nafagrel; D008784:Methysergide