title: Leukotriene D4 receptor blockade inhibits the immediate and late bronchoconstrictor responses to inhaled antigen in patients with asthma.
abstract: We have tested the hypothesis that leukotriene D4 (LTD4) receptor activation is involved in the development of antigen-induced bronchoconstriction. In two studies, patients with asthma received infusions of placebo or MK-571, a potent and specific LTD4 receptor antagonist (450 mg or 37.5 mg total dose, respectively). Antigen was inhaled during test-drug administration, and FEV1 was measured for 10 hours after challenge. Urine samples were collected for measurement of LTE4; plasma samples were drawn repeatedly for assay of MK-571. MK-571 infusions inhibited both immediate (0 to 3 hours) and late (3 to 10 hours) asthmatic responses. For the high MK-571 dose, the extent of inhibition, as assessed by the area under the curve of FEV1 versus time was 88% (p = 0.01) and 63% (p = 0.01), for immediate and late responses, respectively. The low MK-571 dose also inhibited both responses but to a minor extent. Mean urinary LTE4 excretion was elevated after antigen challenge and was unaffected by administration of the LTD4 receptor antagonist. The present study demonstrates that MK-571 inhibits antigen-induced asthma in a dose-related fashion; it had not effect on antigen-induced increases in urinary LTE4 excretions. The results suggest that LTD4 receptor activation plays an important role in antigen-induced asthma.
authors.affiliation: Department of Pulmonary Medicine, Malmö General Hospital, Sweden.
authors.forename: J B
authors.initials: JB
authors.lastname: Rasmussen
authors.forename: L O
authors.initials: LO
authors.lastname: Eriksson
authors.forename: D J
authors.initials: DJ
authors.lastname: Margolskee
authors.forename: P
authors.initials: P
authors.lastname: Tagari
authors.forename: V C
authors.initials: VC
authors.lastname: Williams
authors.forename: K E
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000941:Antigens / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D016084:Bronchoconstriction / Q000276:immunology*; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D017999:Leukotriene E4; D008297:Male; D011422:Propionates / Q000097:blood / Q000494:pharmacology; D011804:Quinolines / Q000097:blood / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism*; D018077:Receptors, Leukotriene; D013189:SRS-A / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000652:urine
chemical_list: D000941:Antigens; D011422:Propionates; D011804:Quinolines; D011971:Receptors, Immunologic; D018077:Receptors, Leukotriene; D013189:SRS-A; C059141:verlukast; D017999:Leukotriene E4; D003404:Creatinine