THE INHIBITION OF [H-3] LEUKOTRIENE D4 BINDING TO GUINEA-PIG LUNG MEMBRANES - THE CORRELATION OF BINDING-AFFINITY WITH ACTIVITY ON THE GUINEA-PIG ILEUM

Guinea-pig lung membranes contain high affinity (KD = 0.8 nM) binding sites for [3H]leukotriene D4 ([3H]LTD4). The binding is inhibited by leukotriene antagonists, such as ICI 198615 and SK & F 104353, in a manner consistent with the Law of Mass Action at a single site. It is also inhibited by a range of leukotriene analogues in a dose-related manner. Inhibition by some of these e.g. LTC4 suggests that the [3H]LTD4 binding sites are heterogeneous. The binding affinity of the leukotriene analogues is significantly correlated (P < 0.001) to their spasmogenic activity on guinea-pig ileum but not on guinea-pig lung strip. The binding affinity of the leukotriene antagonists is also correlated to their antagonist activity on guinea-pig ileum (P < 0.05) but not on guinea-pig lung. These results indicate that the [3H]LTD4 binding site in guinea-pig lung is similar to the leukotriene receptor activated by LTD4 and LTE4 on guinea-pig ileum. The contractile response of guinea-pig lung strips to leukotrienes, in the presence of indomethacin, is mediated by a distinct type of leukotriene receptor. © 1990.