The binding of [3H]leukotriene C4 to guinea-pig lung membranes. The lack of correlation of LTC4 functional activity with binding affinity

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

doi:10.1016/0014-2999(87)90456-0

Cited by 31 publications

(7 citation statements)

References 26 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: 63%

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

et al. 2003

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Section: Cyslt Radioligand Binding Studiesmentioning

confidence: 63%

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

et al. 2003

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“…For example, the contradictory results of previous reports on the effects of CysLT 1 receptor antagonists on LTD 4 ‐induced contractions in ovine airways ( Tomioka et al ., 1991 ; Wikström Jonsson, 1997 ) may relate to the use of S‐hexyl GSH in the latter study. In addition, S‐decyl GSH is commonly used as an inhibitor of non‐receptor binding in agonist binding studies using radioactive cysteinyl‐leukotrienes ( Norman et al ., 1987 ; Takasaki et al ., 2000 ). Ravasi et al .…”

Section: Discussionmentioning

confidence: 99%

An alternative pathway for metabolism of leukotriene D₄: effects on contractions to cysteinyl‐leukotrienes in the guinea‐pig trachea

Bäck

Kumlin

Cotgreave

et al. 2001

British J Pharmacology

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1 Contractions of guinea-pig tracheal preparations to cysteinyl-leukotrienes (LTC 4 , LTD 4 and LTE 4 ) were characterized in organ baths, and cysteinyl-leukotriene metabolism was studied using radiolabelled agonists and RP-HPLC separation. 2 In the presence of S-hexyl GSH (100 mM) the metabolism of [ (1 ± 10 nM) with a pA 2 -value of 9.3+0.2. However, at higher concentrations of ICI 198,615 (30 ± 300 nM) a residual contraction to LTD 4 was unmasked, and this response was inhibited by BAY u9773 (1 ± 3 mM). 4 In the presence of the combination of S-hexyl GSH with L-cysteine, the LTD 4 -induced contractions displayed the characteristics of the LTC 4 contractile responses, i.e. resistant to CysLT 1 receptor antagonism, increased maximal contractions and slower time-course. This qualitative change of the LTD 4 -induced contraction was also observed in the presence of S-decyl GSH (100 mM), GSH (10 mM) and GSSG (10 mM). 5 S-hexyl GSH, S-decyl GSH, GSH and GSSG all stimulated a formation of [

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“…Moreover, it is well known that in cellular membranes, LTC 4 binds predominantly to a number of nonreceptor sites, such as glutathione-S-transferase (Metters et al, 1994;Sun et al, 1986), LTC 4 synthase (Nicholson et al, 1992), or transport proteins (Keppler, 1992). Therefore, we used S-decyl-GSH, a ligand structurally similar to LTC 4 but devoid of either agonist or antagonist activities (Norman et al, 1987;Sala et al, 1990), to inhibit binding to such nonreceptor sites and thus unmask a putative high affinity LTC 4 receptor. In fact, because LTC 4 is able to contract human isolated lung strips with a potency similar to LTD 4 (Gardiner and Cuthbert, 1988), it is likely that LTC 4 , as well as LTD 4 , should have a high affinity binding site.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Two Cysteinyl-Leukotriene High Affinity Binding Sites with Receptor Characteristics in Human Lung Parenchyma

et al. 1998

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We report the characterization of two distinct binding sites with receptor characteristics for leukotriene (LT)D4 and LTC4 in membranes from human lung parenchyma. The use of S-decyl-glutathione allowed us to characterize a previously unidentified high affinity binding site for LTC4. Computerized analysis of binding data revealed that each leukotriene interacts with two distinct classes of binding sites (Kd = 0.015 and 105 nM for LTC4 and 0.023 and 230 nM for LTD4) and that despite cross-reactivity, the two high affinity sites are different entities. LTD4 binding sites displayed features of G protein-coupled receptors, whereas LTC4 binding sites did not show any significant modulation by guanosine-5'-(beta, gamma-imido)triphosphate or stimulation of GTPase activity. The antagonists ICI 198,615 and SKF 104353 were unselective for the high and low affinity states of LTD4 receptor, whereas only SKF 104353 was able to recognize the two [3H]LTC4 binding sites although with different affinities. These data indicate that in human lung parenchyma, LTD4 and LTC4 recognize two different binding sites; these binding sites are different entities; and for LTD4, the two binding sites represent the interconvertible affinity states of a G protein-coupled receptor, whereas for LTC4, the high affinity site is likely to be a specific LTC4 receptor.

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The binding of [3H]leukotriene C4 to guinea-pig lung membranes. The lack of correlation of LTC4 functional activity with binding affinity

Cited by 31 publications

References 26 publications

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

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

An alternative pathway for metabolism of leukotriene D₄: effects on contractions to cysteinyl‐leukotrienes in the guinea‐pig trachea

Identification and Characterization of Two Cysteinyl-Leukotriene High Affinity Binding Sites with Receptor Characteristics in Human Lung Parenchyma

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The binding of [3H]leukotriene C4 to guinea-pig lung membranes. The lack of correlation of LTC4 functional activity with binding affinity

Cited by 31 publications

References 26 publications

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

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

An alternative pathway for metabolism of leukotriene D4: effects on contractions to cysteinyl‐leukotrienes in the guinea‐pig trachea

Identification and Characterization of Two Cysteinyl-Leukotriene High Affinity Binding Sites with Receptor Characteristics in Human Lung Parenchyma

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An alternative pathway for metabolism of leukotriene D₄: effects on contractions to cysteinyl‐leukotrienes in the guinea‐pig trachea