Corpus ID: 2755327

Inhibition of 3H-leukotriene D4 binding to guinea pig lung receptors by the novel leukotriene antagonist ICI 198,615.

  title={Inhibition of 3H-leukotriene D4 binding to guinea pig lung receptors by the novel leukotriene antagonist ICI 198,615.},
  author={David Aharony and R C Falcone and Robert D. Krell},
  journal={The Journal of pharmacology and experimental therapeutics},
  volume={243 3},
The specific binding of [3H]5(S)hydroxy-6(R)-S-cysteinylglycyl -7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid ([3H]LTD4) to receptors on guinea pig lung parenchymal membranes and its inhibition by ICI 198,615, a representative example of a new class of leukotriene antagonists, was characterized by a receptor-ligand binding assay. [3H]LTD4 bound specifically and rapidly (Kon = 0.29 +/- 0.6 nM-1.min-1) reaching equilibrium within 15 min. The rate of binding was greatly inhibited in the presence of… Expand
Specific binding of 3H-ICI 198,615, a potent LTD4 antagonist, to guinea pig cardiac ventricular membranes.
Evidence is provided supporting the existence of specific and high affinity binding sites for 3H-ICI 198,615 in GPCVM. Expand
The inhibition of [3H]leukotriene D4 binding to guinea-pig lung membranes. The correlation of binding affinity with activity on the guinea-pig ileum.
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. Expand
Assessment of leukotriene D4 receptor antagonists.
  • D. Aharony
  • Biology, Medicine
  • Methods in enzymology
  • 1990
Although these binding assays are highly efficient, rapid, and possess high capacity to test antagonist potency and mechanism, they do not provide broad pharmacological information as do functional receptor assays that utilize viable tissues. Expand
The preclinical pharmacology of ICI 204,219. A peptide leukotriene antagonist.
The compound inhibited LTD4- and LTE4-induced increases in cutaneous vascular permeability in guinea pigs, being 1,006- and 679-fold more potent than the first generation LT antagonists LY 171,883 and FPL 55712, respectively. Expand
In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues.
In vitro studies indicate that ONO-1078 is a highly potent, selective and competitive antagonist of peptide leukotrienes that acts with higher affinity at LTD4 and LTE4 receptors than LTC4 receptors. Expand
Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma.
A heterogeneity of binding sites for ICI 198,615 in membranes from human lung parenchyma is indicated and this novel compound is a very potent and selective antagonist of LTD4 receptors in this tissue. Expand
Biochemical and pharmacological characterization of ICI 198,615: a peptide leukotriene receptor antagonist.
The compound both inhibited and reversed aerosol ovalbumin antigen-induced increases in pulmonary resistance in passively sensitized guinea pigs, but demonstrated little ability to inhibit or reverse ovalbum in antigen- induced decreases in dynamic lung compliance. Expand
Characterization of the leukotriene D4 receptor in hyperreactive rat lung.
Ki values show that agonists, but not antagonists, compete for leukotriene D4 binding in rat lung with the same potency as they compete for [3H]leukotRIene D 4 binding in guinea-pig lung, the classical tissue for leukaemia D4 receptor studies. Expand
Pharmacological characterization of the cysteinyl‐leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro
The results of the present in vitro investigation indicate that iralukast and CGP 57698 are potent antagonists of LTD4 in human airways, with affinities in the nanomolar range, similar to those obtained for ICI 204,219 and ONO 1078, two of the most clinically advanced CysLT receptor antagonists. Expand
Inhibition of antigen-induced contraction of guinea pig trachea by ICI 198,615.
In guinea pig trachea, leukotrienes, in combination with other lipoxygenase metabolites, mediate a major part of the response to antigen, in contrast to PAF, histamine and prostaglandins, which appear to play only a minor role. Expand