Identification and characterization of two cysteinyl-leukotriene high affinity binding sites with receptor characteristics in human lung parenchyma

We report the characterization of rwo distinct binding sites with receptor characteristics for leukotriene (LT)D-4 and LTC4 in membranes from human lung parenchyma. The use of S-decylglutathione allowed us to characterize a previously unidentified high affinity binding site for LTC4. Computerized analysis of binding data revealed that each leukotriene interacts with two distinct classes of binding sites (K-d= 0.015 and 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites are different entities. LTD4 binding sites displayed features of G protein-coupled receptors, whereas LTC4 binding sites did not show any significant modulation by guanosine-5'-(beta&GAMMA-imido)triphosphate of stimulation of GTPase activity. The antagonists ICI 198, 615 and SKF 104353 were unselective for the high and low affinity states of LTD4 receptor, whereas only SKF 10453 was able to recognize the two [H-3]LTC4 binding sites although with different affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4 recognize two different binding sites; these binding sites are different entities; and for LTD4, the two binding sites represent the inconvertible affinity states of a G-protein-coupled receptor, whereas for LTC4, the high affinity site is likely to be a specific LTC4 receptor.