Effect of indomethacin on airway contraction and the release of LTC4-like material.
Ovalbumin (OA) and arachidonic acid (AA) were used to induce contractions of sensitized guinea-pig tracheal and lung preparations in the presence and absence of indomethacin. Leukotriene (LT)C4-like material released from these tissues was extracted from the bathing fluid and measured by radioimmunoassay. Challenge with either OA or AA induced release of LTC4-like material from both parenchyma and trachea, AA inducing a greater release than OA although OA induced greater contractions. This suggested that OA-induced the synthesis of other bronchoconstrictor compounds than LTC4. Although indomethacin enhanced OA- and AA-induced contractions of trachea, there was no enhancement of the release of LTC4-like material, suggesting enhancement by indomethacin was a result of the inhibition of the synthesis of prostaglandin E2 and not diversion of AA into the lipoxygenase pathway. Indomethacin had no effect on OA-induced contractions of parenchyma, but attenuated those induced by AA. Indomethacin had no modulatory effect on the release of LTC4-like material in the parenchyma. The results demonstrate that indomethacin does not result in increased synthesis of LTs in the airways.
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008168:Lung / Q000276:immunology* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000502:physiology; D010047:Ovalbumin / Q000276:immunology; D013189:SRS-A / Q000378:metabolism*; D014132:Trachea / Q000502:physiology
D001095:Arachidonic Acids; D013189:SRS-A; D016718:Arachidonic Acid; D010047:Ovalbumin; D007213:Indomethacin