Characterization of a leukotriene D4 receptor in guinea pig lung.

Publisher Website
Google Scholar
Abstract
[3H]Leukotriene [LT] D4 bound, in a saturable manner and with exceedingly high affinity, to a membrane preparation from guinea pig lung. Measurement of saturation at equilibrium yielded Kd values of 5.46 .+-. 0.31 .times. 10-11 M at 20.degree. C and 2.12 .+-. 0.37 .times. 10-10 M at 0.degree. C while the numbers of binding sites (Bmax) were 384 .+-. 34 and 302 .+-. 44 fmol/mg protein at 20 and at 0.degree. C, respectively. The time courses of both association and dissociation were slow, but the rate of dissociation was accelerated by either NaCl or GTP. Binding was enhanced by Ca2+, Mg2+ and Mn2+ and inhibited by Na+ but not by Li+ or K+, suggesting that the binding of LTD4 may be regulated by ions. LTE4, but not LTC4, had a high affinity for the putative receptor, consistent with the pharmacological evidence that the actions of LTD4 and E4 are mediated by a receptor distinct from that for LTC4. Affinities of stereoisomers and related compounds for the LTD4 binding sites closely paralleled their contractile activities in guinea pig lung parenchymal strips. The antagonist of slow-reacting substance of anaphylaxis, FPL 55712 [7-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxy)-2-hydroxypropoxy]-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid monosodium salt] inhibited the binding of [3H]LTD4 with a Ki value of 1 .times. 10-7 M, which is in agreement with reported Kb values obtained in pharmacological studies.