Reversal of leukotriene D4- and leukotriene E4-induced airway constriction in the guinea pig.
Conscious Hartley guinea pigs were challenged with LTD4 or LTE4 aerosols. When dynamic compliance (Cdyn) decreased to 50% of its baseline value, the challenge aerosols were stopped and treatment aerosols of salbutamol, the LTD4/E4 antagonist LY171883 Na, atropine, or sodium chloride (control) were begun. After 5 min of continuous exposure to the treatment aerosol, each animal was killed and excised lung gas volume (ELGV) was measured. Salbutamol was equally effective in reversing LTD4- and LTE4-induced Cdyn changes. Aerosolized LY171883 Na was effective against both agonists, but was about threefold more potent against LTE4. In contrast, atropine was very effective in reversing LTD4-induced Cdyn changes, but produced minimal reversal when LTE4 was the challenge agent. Pulmonary gas trapping results supported these observations; ELGV values were closely correlated with 5-min Cdyn measurements for both LTD4 (r = -0.817) and LTE4 (r = -0.831). Thus, although LTD4 and LTE4 are though to act on the same or similar receptors, the pattern of pharmacologic reversal at comparable levels of airway obstruction differs for these two agonists.
Silbaugh
S A
SA
Department of Immunology, Pulmonary and Leukotriene Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
Stengel
P W
PW
Pechous
P A
PA
Marshall
W S
WS
D000098:Acetophenones / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D012898:Autacoids / Q000037:antagonists & inhibitors; D001980:Bronchi / Q000187:drug effects* / Q000502:physiology; D006168:Guinea Pigs; D017999:Leukotriene E4; D008170:Lung Compliance / Q000187:drug effects; D008176:Lung Volume Measurements; D008297:Male; D012119:Respiration / Q000187:drug effects; D013189:SRS-A / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
D000098:Acetophenones; D012898:Autacoids; D013189:SRS-A; D013777:Tetrazoles; D017999:Leukotriene E4; D001285:Atropine; C044660:LY 171883; D000420:Albuterol