The inhibition of [3H]leukotriene D4 binding to guinea-pig lung membranes. The correlation of binding affinity with activity on the guinea-pig ileum

Norman, Peter; Abram, Trevor S.; Cuthbert, Nigel J.; Gardiner, P.J.

doi:10.1016/0014-2999(90)90289-i

Cited by 20 publications

(7 citation statements)

References 19 publications

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“…In addition, recent binding studies (Ravasi et al, 2000) have also suggested the necessity to include S-decyl-glutathione (a high-affinity ligand for nonreceptor LTC 4 binding sites) in the membrane preparations. Second, there was often no correlation between the [ 3 H]LTC 4 binding studies and the functional studies (contraction) as in the case of either the guinea pig ileum (Norman et al, 1990), guinea pig lung strip Norman et al, 1987), or guinea pig uterus (Weichman and Tucker, 1982;Levinson, 1984). In contrast, a correlation was observed between the antagonist effects in the [ 3 H]LTD 4 binding studies and the ability of the antagonists to block LTD 4 -induced contractions (Fig.…”

Section: Cyslt Radioligand Binding Studiesmentioning

confidence: 62%

“…However, LTE 4 was markedly less active than LTC 4 and LTD 4 in these tissues (Buckner et al, 1986). A comparison of the cys-LT agonist potencies between different tissues illustrates that considerable variation exists in functional assays (pEC 50 values 11 to 7) (Jones et al, 1984;Hand and Schwalm, 1987;Gieske et al, 1990;Norman et al, 1990;DeLegge et al, 1993). Based solely upon agonist potencies, one is unable to surmise whether either a single or several receptors are present in these preparations.…”

Section: B Cysteinyl-leukotriene Functional Studiesmentioning

confidence: 99%

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International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

et al. 2003

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Section: Cyslt Radioligand Binding Studiesmentioning

confidence: 62%

Section: B Cysteinyl-leukotriene Functional Studiesmentioning

confidence: 99%

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

et al. 2003

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“…Other ligand binding assays The specific binding of [ 3 H]‐5′‐N‐ethylcarboxamidoadenosine (adenosine, non‐selective), [ 3 H]‐prazosin (α 1 ‐adrenoceptors, non‐selective), [ 3 H]‐quinuclidi‐nylbenzilate (muscarinic, non‐selective), [ 3 H]‐pyrilamine (his‐tamine, H 1 ), [ 125 I]‐endothelin‐l (endothelin‐1 ET A ), [ 3 H]‐substance P (neurokinin, NK 1 ), [ 3 H]‐leukotriene D 4 (leuko‐triene, cysLT 1 ) were assayed according to the methods of Brans et al (1986), Reader et al (1987), Luthin & Wolfe (1984), Haaksma et al (1990), Ambar et al (1989), McLean et al (1993) and Norman et al (1990), respectively. The receptor sources of these binding assays are bovine striatal membranes, rat forebrain membranes, guinea‐pig bladder membranes, bovine cerebellar membranes, A10 cells, rat submaxillary gland membranes and guinea‐pig lung membranes, respectively.…”

Section: Methodsmentioning

confidence: 99%

The identification of an orally active, nonpeptide bradykinin B₂ receptor antagonist, FR173657

Asano¹,

Inamura²,

Hatori³

et al. 1997

British J Pharmacology

112

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An orally active, nonpeptide bradykinin (BK) B2 receptor antagonist, FR173657 (E)‐3‐(6‐acetamido‐3‐pyridyl)‐N‐[N‐[2‐4‐dichloro‐3‐[(2‐methyl‐8‐quinolinyl) oxymethyl]phenyl]‐N‐methylaminocarbonyl‐methyl]acrylamide) has been identified. This compound displaced [3H]‐BK binding to B2 receptors present in guinea‐pig ileum membranes with an IC50 of 5.6 × 10−10 M and in rat uterus with an IC50 of 1.5 × 10−9 M. It did not inhibit different specific radio‐ligand binding to other receptor sites. In human lung fibroblast IMR‐90 cells, FR173657 displaced [3H]‐BK binding to B2 receptors with an IC50 of 2.9 × 10−9 M and a Ki of 3.6 × 10−10 M, but did not reduce [3H]‐des‐Arg10‐kallidin binding to B1, receptors. In guinea‐pig isolated preparations, FR173657 antagonized BK‐induced contractions with an IC50 of 7.9 × 10−9 M, but did not antagonize acetylcholine or histamine‐induced contractions even at a concentration of 10−6 M. FR173657 caused parallel rightward shifts of the concentration‐response curves to BK at concentrations of 10−9 M and 3.2 × 10−9 M, and a little depression of the maximal response in addition to the parallel rightward shift of the concentration‐response curve at a concentration of 10−8 M. Analysis of the data yield a pA2 of 9.2 ± 0.2 (n = 5) and a slope of 1.5 ± 0.2 (n = 5). In vivo, the oral administration of FR173657 inhibited BK‐induced bronchoconstriction dose‐dependently in guinea‐pigs with an ED50 of 0.075 mg kg−1, but did not inhibit histamine‐induced bronchoconstriction even at 1 mg kg−1. FR173657 also inhibited carrageenin‐induced paw oedema with an ED50 of 6.8 mg kg−1 2 h after the carrageenin injection in rats. These results show that FR173657 is a potent, selective, and orally active bradykinin B2 receptor antagonist.

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“…Indomethacin, NDGA and OKY-046•HCl as reference compounds showed potent inhibition with respective IC50 values of 0.13 ± 0.12, 0.25 ± 0.03 and 0.017 ± 0.003,uM (n = 3-5). The existence of multiple LTD4 receptors has been reported in guinea pig ileum and lung parenchymal strips using FPL55712 (32,33). In functional experi ments, the antagonist activity of ONO-1078 against LTD4 in guinea pig trachea (pA2 = 10.71) was approx imately 2.1 log degrees higher than that in guinea pig lung parenchymal strips (pA2 = 8.58).…”

Section: Specificity Of the Action Of Ono-1078mentioning

confidence: 95%

In Vitro Antagonism of ONO-1078, a Newly Developed Anti-Asthma Agent, against Peptide Leukotrienes in Isolated Guinea Pig Tissues.

et al. 1992

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ABSTRACT-We evaluated the antagonist activity of ONO-1078 against peptide leukotrienes (LTs) by a radioligand binding assay and functional experiments in guinea pigs. In the radioligand binding assay, ONO-1078 inhibited [3H]LTD4 and [3H]LTE4 bindings to lung membranes (K; = 0.99 and 0.63 nM, re spectively) and was 2,000 to 3,000-fold more potent than FPL55712. Antagonism of ONO-1078 against [3H]LTC4 binding (K; = 5640 nM) was approximately twofold more potent than that of FPL55712. The antagonism of ONO-1078 against [3H]LTD4 binding was competitive. In functional experiments, ONO 1078 showed competitive antagonism against the LTC4 and LTD4-induced contractions of guinea pig trachea and lung parenchymal strips with a pA2 range of 7.70 to 10.71 and was approximately 400 to 3,300-fold more potent than FPL55712. Interestingly, in the presence of an inhibitor of the bioconver sion of LTC4 to LTD4, ONO-1078 also antagonized the LTC4-induced contraction of guinea pig trachea (pA2 = 7.78). ONO-1078 significantly reversed the LTD4-induced prolonged contraction without effect on the KCl and BaC12-induced contractions of guinea pig trachea. Furthermore, ONO-1078 antago nized the antigen-induced SRS-A mediated contraction of guinea pig trachea. On the other hand, ONO-1078 showed no antagonism against histamine, acetylcholine, 5-hydroxytryptamine, prostaglandin D2 and U-46619. In addition, ONO-1078 showed little or no effect on the activities of cyclooxygenase, 5-lipoxygenase and thromboxane synthetase. These 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.

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The inhibition of [3H]leukotriene D4 binding to guinea-pig lung membranes. The correlation of binding affinity with activity on the guinea-pig ileum

Cited by 20 publications

References 19 publications

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

The identification of an orally active, nonpeptide bradykinin B₂ receptor antagonist, FR173657

In Vitro Antagonism of ONO-1078, a Newly Developed Anti-Asthma Agent, against Peptide Leukotrienes in Isolated Guinea Pig Tissues.

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The inhibition of [3H]leukotriene D4 binding to guinea-pig lung membranes. The correlation of binding affinity with activity on the guinea-pig ileum

Cited by 20 publications

References 19 publications

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

International Union of Pharmacology XXXVII. Nomenclature for Leukotriene and Lipoxin Receptors

The identification of an orally active, nonpeptide bradykinin B2 receptor antagonist, FR173657

In Vitro Antagonism of ONO-1078, a Newly Developed Anti-Asthma Agent, against Peptide Leukotrienes in Isolated Guinea Pig Tissues.

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The identification of an orally active, nonpeptide bradykinin B₂ receptor antagonist, FR173657