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  • Title: Pulmonary actions of LY255283, a leukotriene B4 receptor antagonist.
    Author: Silbaugh SA, Stengel PW, Cockerham SL, Roman CR, Saussy DL, Spaethe SM, Goodson T, Herron DK, Fleisch JH.
    Journal: Eur J Pharmacol; 1992 Nov 13; 223(1):57-64. PubMed ID: 1335877.
    Abstract:
    The actions of LY255283, a leukotriene (LT) B4 receptor antagonist, were examined on guinea pig lung. LTB4 and LY255283 displaced [3H]LTB4 from its binding site on lung membranes with pKi values of 9.9 and 7.0, respectively. In the functional correlate of the binding studies, LY255283 competitively reduced contractile responses of lung parenchyma to LTB4 (pA2 = 7.2). LTB4 produced airway obstruction which was reduced by LY255283 administered i.v. (ED50 = 2.8 mg/kg) or orally (ED50 = 11.0 mg/kg). Contractile responses to histamine, LTD4 and the thromboxane mimetic, U46619, were not reduced by LY255283. The compound also did not inhibit cyclooxygenase or 5-lipoxygenase enzymes. We conclude that LY255283 selectively antagonized pharmacologic responses to LTB4 on lung tissue and appears to be a useful tool to investigate the role of LTB4 in pulmonary disease.
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