title: Identification and characterization of leukotriene D4 receptors in adult and fetal human lung.
abstract: Leukotriene D4 (LTD4) receptors were identified and characterized in adult and fetal human lung membranes. Macroscopically normal adult lung tissue was selected from seventeen surgical biopsy specimens, and twenty-seven fetal lung samples were obtained from therapeutic abortions. Binding assays were performed using pooled adult or fetal human lung membranes at 30 degrees under conditions which prevented metabolism of [3H]LTD4. Specific binding reached equilibrium within 30 min, remained constant for 60 min, was enhanced by Mg2+, and was inhibited by Na+ and guanyl-5'-yl-imidodiphosphate. Computer-assisted analyses of saturation binding data showed a single class of binding sites with similar apparent Kd (0.15 +/- 0.09 and 0.12 +/- 0.003 nM) and Bmax (68 +/- 29 and 62 +/- 14 fmoles/mg protein) values for adult and fetal samples respectively. Competition binding studies with [3H]LTD4 showed the same rank order potency for adult and fetal lung receptors (5S, 6R-LTD4 greater than 5S, 6R-LTD1 greater than 5R, 6S-LTD4 greater than 5S,6R-LTE4 greater than FPL 55712). A comparison of the receptor binding affinities of these compounds with their smooth muscle contractile agonist (pD2) and antagonist (-log[KB]) activities in guinea pig lung and trachea showed a good correlation (r = 0.88), suggesting that the saturable, high-affinity, stereoselective [3H]LTD4 specific binding sites identified in human lung may be physiologically relevant receptor moieties.
mesh_terms: D000328:Adult; D001667:Binding, Competitive; D002867:Chromones / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D011247:Pregnancy; D011869:Radioligand Assay; D011956:Receptors, Cell Surface / Q000032:analysis*; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin / Q000032:analysis*; D013189:SRS-A / Q000378:metabolism; D014316:Tritium
chemical_list: D002867:Chromones; D011956:Receptors, Cell Surface; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; D014316:Tritium; C006312:FPL 55712