Binding of leukotrienes C4 and D4 to membranes from guinea pig lung: regulation by ions and guanine nucleotides.

Tritium-labeled leukotrienes C4 and D4 (LTC4 and LTD4) bind to membranes from guinea pig lung. Binding properties of the two ligands are almost identical. More than 80% of 3H-LTC4 and 3H-LTD4 binding can be blocked by unlabeled LTC4 (IC50 8 nM versus 3H-LTC4 and 8 nM versus 3H-LTD4), LTD4 (12 nM, 16 nM), LTE4 (40 nM, 98 nM), and the leukotriene antagonist FPL 55712 (14 microM, 11 microM). Binding is reversible (50% dissociation at 65 min for both ligands at 25 degrees). Binding of 3H-LTC4 and 3H-LTD4 is enhanced by divalent cations and inhibited by sodium ions, guanine nucleotides, and EDTA. 3H-LTD4 binds in unaltered form, but 3H-LTC4 appears to bind mostly after conversion to 3H-LTD4. The high affinity, reversibility, and regulation by ions and guanine nucleotides of 3H-LTC4 and 3H-LTD4 binding strongly imply that these binding sites are physiological LTD4 receptors.