The contractile activities of lipoxin A4 and lipoxin B4 for guinea-pig airway tissues.
1. The isometric contractile activities of lipoxin A4 (LxA4) and lipoxin B4 (LxB4) were evaluated on guinea-pig lung tissue over the concentration range, 10(-8) to 10(-5) M. 2. LxA4 contracted guinea-pig lung parenchymal strips; the concentration eliciting 50% maximum histamine response was 3 x 10(-6) M. LxA4 did not contract tracheal spirals. 3. The LxA4 dose-response curve was parallel to that of leukotriene D4 (LTD4) with LxA4 being approximately 10,000 fold less potent than LTD4. 4. The time course of the contraction elicited by LxA4 was similar to that of LTD4 and it was slow in onset and did not plateau for 20 min. 5. Pre-incubation of parenchymal strips with leukotriene receptor antagonists at a concentration of 1 x 10(-6) M to 3 x 10(-5) M FPL 55712 or 3 x 10(-5) M L 649923 inhibited LxA4 activity. 6. Pre-incubation of tissues with 1 x 10(-5) M L 651392, a 5-lipoxygenase inhibitor, or 1 x 10(-5) M indomethacin, a cyclo-oxygenase inhibitor, did not affect the contractile activity of LxA4. 7. LxB4 did not constrict parenchymal strips or tracheal spirals.
Jacques
C A
CA
Department of Medicine, United Medical School, Guy's Hospital, London.
Spur
B W
BW
Crea
A E
AE
Lee
T H
TH
D000818:Animals; D002867:Chromones / Q000494:pharmacology; D006168:Guinea Pigs; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007975:Leukotriene B4 / Q000494:pharmacology; D044045:Lipoxins; D016859:Lipoxygenase Inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D013189:SRS-A / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013237:Stereoisomerism; D014132:Trachea / Q000187:drug effects
D002867:Chromones; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D016859:Lipoxygenase Inhibitors; D013189:SRS-A; C040527:lipoxin A4; D007975:Leukotriene B4; C006312:FPL 55712; C042651:lipoxin B4