Leukotriene D4 and platelet-activating factor-acether antagonists on allergic and arachidonic acid-induced reactions in guinea pig airways.
Arachidonic acid (AA) and ovalbumin (OA) were used to induce contractions of sensitized guinea pig tracheal spiral (indomethacin-pretreated) and lung parenchymal strip preparations. This model was used to examine the properties of three leukotriene (LT) D4 antagonists and a platelet-activating factor (PAF)-acether receptor antagonist. The three LTD4 antagonists, L-649,923, FPL 57231, and LY163443, inhibited AA-induced contractions of indomethacin-pretreated tracheal spirals selectively. The PAF-acether antagonist, L-652,731, did not inhibit AA-induced contractions of either trachea or parenchyma. This confirmed that AA-induced contractions of trachea involved release and activity of LTD4. The LTD4 antagonists and L-652,731 partially inhibited OA-induced contractions of both trachea and parenchyma. When L-649,923 and L-652,731 or FPL 57231 and L-652,731 were combined, an additive inhibitory effect on OA-induced contractions was observed. When LY163443 and L-652,731 were combined, the inhibitory effect was synergistic. This may be due to the additional effect of LY163443 to inhibit phosphodiesterase. Total inhibition of OA-induced contractions was obtainable with relatively low concentrations when a LTD4 and PAF-acether antagonist were combined. These results suggested that LTD4 and PAF-acether may be the two major mediators in our model of allergic bronchospasm. The LTD4 and PAF-acether antagonists had the capacity to decrease baseline tone, even on tissues that were already relaxed with indomethacin, suggesting that LTD4 and PAF-acether may contribute to intrinsic tone in airway smooth muscle.
Burka
J F
JF
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, P.E.I., Canada.
Briand
H
H
Scott-Savage
P
P
Pasutto
F M
FM
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000503:physiopathology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010047:Ovalbumin / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D012137:Respiratory System / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D001095:Arachidonic Acids; D010972:Platelet Activating Factor; D013189:SRS-A; D016718:Arachidonic Acid; D010047:Ovalbumin; D007213:Indomethacin