The inhibition of [3H]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 less than 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 less than 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.
Bayer U.K. Limited, Research Department, Stoke Poges, Slough, U.K.
P
P
Norman
T S
TS
Abram
N J
NJ
Cuthbert
P J
PJ
Gardiner
D000818:Animals; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000378:metabolism; D011869:Radioligand Assay; D013189:SRS-A / Q000378:metabolism*
D007202:Indicators and Reagents; D013189:SRS-A; D007213:Indomethacin