The binding of [3H]leukotriene C4 to guinea-pig lung membranes. The lack of correlation of LTC4 functional activity with binding affinity.
High affinity binding sites for [3H]leukotriene C4 ([3H]LTC4) have been identified and characterised in guinea-pig lung membranes. [3H]LTC4 bound to these membranes with a pharmacological specificity totally distinct to that previously observed for [3H]LTD4 binding in guinea-pig lung. Scatchard analysis of saturation binding data showed a single class of binding sites, with a dissociation constant (KD) of 52.6 +/- 4.9 nM and a density (Bmax) of 30 +/- 12 pmol/mg membrane protein. The binding was inhibited with high affinity by a variety of glutathione-containing leukotriene analogues. Most notable was the inhibition by 1,2,3,4-tetranor LTC4 (Ki = 118 nM) and S-decylglutathione (Ki = 154 nM) since neither of these compounds were contractile agonists on guinea-pig parenchymal strips or guinea-pig ileum nor were they antagonists of LTC4-induced contractions of these smooth muscle preparations. These results indicate that the observed binding of [3H]LTC4 to guinea-pig lung membranes is not to a contractile receptor.
Norman
P
P
Miles Laboratories Ltd., Stoke Poges, Slough, U.K.
Abram
T S
TS
Kluender
H C
HC
Gardiner
P J
PJ
Cuthbert
N J
NJ
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D006168:Guinea Pigs; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism; D013189:SRS-A / Q000378:metabolism*
D013189:SRS-A