IDENTIFICATION AND CHARACTERIZATION OF 2 CYSTEINYL-LEUKOTRIENE HIGH-AFFINITY BINDING-SITES WITH RECEPTOR CHARACTERISTICS IN HUMAN LUNG PARENCHYMA

We report the characterization of rwo distinct binding sites with rece ptor characteristics for leukotriene (LT)D-4 and LTC4 in membranes fro m human lung parenchyma. The use of S-decylglutathione allowed us to c haracterize a previously unidentified high affinity binding site for L TC4. Computerized analysis of binding data revealed that each leukotri ene interacts with two distinct classes of binding sites (K-d= 0.015 a nd 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cro ss-reactivity, the two high affinity sites are different entities. LTD 4 binding sites displayed features of G protein-coupled receptors, whe reas LTC4 binding sites did not show any significant modulation by gua nosine-5'-(Β&GAMMA-imido)triphosphate of stimulation of GTPase ac tivity. The antagonists ICI 198, 615 and SKF 104353 were unselective f or 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 pare nchyma, LTD4 and LTC4 recognize two different binding sites; these bin ding sites are different entities; and for LTD4, the two binding sites represent the inconvertible affinity states of a G-protein-coupled re ceptor, whereas for LTC4, the high affinity site is likely to be a spe cific LTC4 receptor.