Lung tissue receptors for sulfidopeptide leukotrienes

Abstract

Studies of the binding of tritiated sutfidopeptide leukotrienes (LTs) to a membrane preparation from rat lung tissue revealed a site specific for LTC 4 with a dissociation constant of 4.1 × 10 −8M. Similar experiments with a guinea pig lung preparation demonstrated binding specific for LTD 4 with a dissociation constant of 2.1 × 10 −10M. The divalent cations Ca ++, Mg ++, and Mn ++ significantly enhanced the affinity of binding of the respective LTs to both sites. The binding of LTC 4 to guinea pig lung and rat lung exhibited similar characteristics, but the former was observed only in the presence of the γ-glutamyl transpeptidase inhibitor, serineborate complex. The binding affinities of various isomers of both sulfidopeptide LTs paralleled the potency of their pharmacologic effects, which supports the contention that the sites are receptors specific for LTC 4 and LTD 4. The slow-reacting substance of anaphylaxis antagonist, FPL 557112, had a higher affinity for the LTD 4 receptor, which is consistent with its more effective antagonism of the LTD 4-induced contractile response of guinea pig lung parenchymal strips. The ability of Na + and guanosine triphosphate to inhibit the binding of LTD 4 suggests that the action of LTD 4 is associated with a depression of intracellular concentrations of cyclic adenosine monophosphate.