Mediators of arachidonic acid-induced contractions of indomethacin-treated guinea-pig airways: leukotrienes C4 and D4

Abstract

Arachidonic acid (AA) (66 microM) induced contractions of indomethacin-treated (8.4 microM) guinea-pig tracheal and lung parenchymal preparations. Mepacrine (210 microM) treatment did not affect the magnitude of contraction induced by AA. Normal and ovalbumin-sensitized tissues responded identically to AA, and released equivalent amounts of the contractile mediators. Nordihydroguaiaretic acid (100 microM) markedly reduced release of the contractile mediators and reduced AA-induced contractions of the airways. The mediators of AA-induced, calcium ionophore A23187-induced, and antigen-induced contraction of the trachea and lung parenchyma were purified and identified by reverse-phase high performance liquid chromatography to be leukotrienes C4 and D4, being present in an approximate ratio of 20:1. Mepacrine-treated trachea exhibited a smaller contractile response to stimuli (A23187 for normal tissues and ovalbumin for sensitized tissues). Addition of exogenous AA (66 microM) increased the magnitude of contraction, although not to the level observed on tissues not treated with mepacrine. There was no observable effect of AA on the response of mepacrine-treated parenchyma to the ionophore or antigen. It was concluded that (a) immunological sensitization does not alter AA metabolism via the lipoxygenase pathway in guinea-pig airways and (b) the mediators of AA-induced contraction are leukotrienes C4 and D4.