Identification and characterization of leukotriene D4 receptors in adult and fetal human lung.
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.
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
D002867:Chromones; D011956:Receptors, Cell Surface; D018077:Receptors, Leukotriene; D011982:Receptors, Prostaglandin; D013189:SRS-A; D014316:Tritium; C006312:FPL 55712