ISSN:
1365-2222
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Background and objective To investigate the role of arachidonic acid (AA) metabolites in airway hypersensitivity.Method We studied the change in airway responsiveness to acetylcholine (ACh) after inhalation of some AA metabolites in guinea-pigs.Results Exposure to prostaglandin (PG) D2, thromboxane (TX) A2 mimetic U-46619, leukotriene (LT) D4 or LTE4 at concentrations which did not influence bronchial tone and blood pressure dose-dependently caused airway hyperresponsiveness. However, the change was not observed after challenge with a high concentration of PGF2α Furthermore, PGD2 and U-46619 induced an acute and short-lived increase in responsiveness, while LTD4 and LTE4 induced a slow-onset and longer-lived increase. In the tachyphyiaxis study, although the tachyphylaxis for airway hyperresponsiveness provoked by PGD2 and U-46619 was not observed, airway hyperresponsiveness induced by the second LTD4 tended to decrease, and the second LTE4-induced airway hyperresponsiveness obviously diminished. In the study using antagonists and inhibitors, TX-receptor antagonist BM-13177 inhibited PGD2- and U-46619-, but not LTD4- and LTE4-induced airway hyperresponsiveness. TX synthase inhibitor OKY-046 had no effect on PGD2-, U-46619- and LTD4-induced airway hyperresponsiveness, while LTE4-induced airway hyperresponsiveness tended to be inhibited by these inhibitors. However, the LT-receptor antagonist ONO-1078 inhibited both LTD4- and LTE4-, but not PGD2- or U-46619-induced airway hyperresponsiveness. 5-lipoxygenase inhibitor AA-861 tended to prevent LTE4-induced airway hyperresponsiveness, but had no effect on PGD2-, U-46619- and LTD4-induced enhanced responses.Conclusion These findings indicate that the local existence of PGD2, TXA2, LTD4 and LTE4 in the guinea-pig airway may act as an airway hyperresponsiveness- inducing factor rather than as a bronchoconstrictor. In addition, PGD2/U-46619 may stimulate the TX receptor to induce an acute and short-lived airway hyperresponsiveness, and LTD4 and LTE4, which may involve secondary mediator release, may act at the LT receptor to induce a slow-onset and longer-lived airway hyperresponsiveness, which may be associated with the induction, the development and the long duration of airway hyperreactivity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1365-2222.1996.tb00633.x
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