Leukotriene B4 and 20-hydroxyleukotriene B4 contract guinea-pig trachea strips in vitro.
In contrast to its established myotropic effect on guinea-pig lung parenchyma, the myotropic action of leukotriene B4 on the trachea is uncertain. Our characterization of its effects on the latter organ indicates that leukotriene B4 contracts guinea-pig trachea zig-zag strips in a concentration-dependent manner from 5 X 10(-9) to 5 X 10(-7) M. Leukotriene B4 was at least 10 times more potent than histamine, but 10 times less potent than leukotriene C4. Similar effects were evident with 20-hydroxyleukotriene B4; however, this metabolite contracted the trachea less forcefully. Tracheas developed tachyphylaxis after cumulative administration of leukotriene B4, but not 20-hydroxyleukotriene B4. The myotropic effect of leukotriene B4 was attributable to an indirect mechanism involving formation of cyclooxygenase metabolites of arachidonic acid. For example, the levels of prostaglandin E2 and prostaglandin F2 alpha released into the incubation medium correlated with the contractile response, and suppression of their biosynthesis with cyclooxygenase inhibitors eliminated that response. We conclude that myotropic effects of leukotriene B4 occur in central airways in addition to peripheral airways. The contribution of leukotriene B4 to tracheal bronchospasm is not necessarily negligible.
D000818:Animals; D015237:Dinoprost; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011460:Prostaglandins F / Q000032:analysis; D013618:Tachyphylaxis / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*
D011460:Prostaglandins F; D007975:Leukotriene B4; C031571:5,12,20-trihydroxy-6,8,10,14-eicosatetraenoic acid; D006632:Histamine; D015237:Dinoprost