Inhibition by REV-5901 of leukotriene release from guinea-pig and human lung tissue in vitro

Kusner, Edward J.; Marks, Rebecca L.; Aharony, David; Krell, Robert D.

doi:10.1016/0006-2952(89)90513-3

Cited by 19 publications

(10 citation statements)

References 34 publications

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“…A prediction of this hypothesis is that inhibition of 5'-lipoxygenase activity should inhibit the response to stimulation of capsaicin-sensitive nerves. Indeed, the 5'-lipoxygenase inhibitor REV 5901, which inhibits the formation of leukotrienes with a dissociation constant (Kd) of -10 tM (Kusner, Marks, Aharony & Krell, 1989), inhibited the magnitude and duration of the second phase. This interpretation should be considered with caution, however, as REV 5901 has also been shown to have some peptidoleukotriene receptor antagonist activity, albeit much less potent in this regard than the other antagonists used in the study (Van Inwegen, Khandwala, Gordon, Sonnino, Coutts & Jolly, 1987).…”

Section: Discussionmentioning

confidence: 99%

Role of peptidoleukotrienes in capsaicin‐sensitive sensory fibre‐mediated responses in guinea‐pig airways.

Ellis¹,

Undem²

1991

The Journal of Physiology

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SUMMARY1. The right bronchus with the right vagus nerve remaining intact was isolated from the guinea-pig. Stimulating the end of the right vagus nerve distal to the bronchus resulted in a biphasic contractile response with a rapid first phase and a second phase which persisted after the cessation of stimulation. The first phase was selectively sensitive to atropine, while the second phase was non-cholinergic, but abolished by pre-treatment with the sensory C fibre toxin, capsaicin. This biphasic contraction was mimicked by electrical field stimulation of the bronchus and strips of the distal aspect of the trachea.2. The capsaicin-sensitive second phase produced by either vagus nerve stimulation or electrical field stimulation, was inhibited by greater than 50% by the selective peptidoleukotriene receptor antagonist SKF 104353, whereas the inactive stereoisomer of SKF 104353, SKF 104373, was without effect. SKF 104353 did not inhibit the cholinergic first phase, nerve conduction along the vagus nerve, or contractions to exogenously added substance P and neurokinin A.3. The inhibitory effect of SKF 104353 on second-phase contractions was mimicked by two structurally unrelated selective peptidoleukotriene receptor antagonists, WY 48252 and ICI 198615, and by the 5'-lipoxygenase inhibitor REV 5901.4. Exogenously added leukotriene D4 (1 nM) potentiated the second-phase contractions in the trachea and this effect was reversed by 041 /SM-SKF 104353.Leukotriene D4 did not affect responses to exogenously added substance P or neurokinin A.5. Stimulation of the right vagus nerve produced plasma extravasation in the trachea and in the main bronchi of atropine-and propranolol-pre-treated guinea-pigs. This was inhibited by about 50% by SKF 104353 (10 mg/kg, i.v.), whereas SKF 104373 (10 mg/kg, i.v.) was without effect.6. It is suggested that endogenous peptidoleukotrienes make a significant contribution to the airway smooth muscle and vascular effects of capsaicin-sensitive nerve stimulation in the guinea-pig.

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Section: Discussionmentioning

confidence: 99%

Role of peptidoleukotrienes in capsaicin‐sensitive sensory fibre‐mediated responses in guinea‐pig airways.

Ellis¹,

Undem²

1991

The Journal of Physiology

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“…(at 2000 h on Day 2 and at 0800 h and 1200 h on Day 3 [15]), or with NDGA, 10 mg/100 g BW i.p. (at 2000 h on Day 2 and at 0800 h and 1600 h on Day 3 [16,17]). …”

Section: Methodsmentioning

confidence: 97%

Possible Role of Platelet-Activating Factor in Embryonic Signaling during Oviductal Transport in the Hamster1

Velásquez

Aguilera

Croxatto³

1995

Biology of Reproduction

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Hamster embryos enter the uterus in pregnant females nearly one day earlier than unfertilized eggs in cycling females. The hypothesis that a substance derived from eicosanoids is released by the embryos, but not by oocytes, to hasten their transport to the uterus was tested by examining the effects of indomethacin, nordihydroguaiaretic acid (NDGA), platelet-activating factor (PAF), and PAF antagonists on egg transport in the hamster. Administration of indomethacin had no effect on embryo transport, whereas administration of NDGA delayed the transport of eggs to the uterus in pregnant but not in cycling hamsters. The PAF antagonists TCV-309 and BN-52021 delayed significantly the transport of eggs to the uterus in pregnant animals, but not in cycling animals; i.e., they retarded the passage of embryos but not of oocytes to the uterus. Administration of PAF to cycling hamsters hastened the oviductal transport of ova. These data suggest that, in the hamster, the earlier passage of embryos to the uterus as compared to oocytes is mediated by PAF. Thrombocytopenia was detected in early-pregnant hamsters, and PAF-like activity was detected in spent media of two-cell through morula stage hamster embryos. These results suggest that preimplantation hamster embryos produce PAF-like activity that mediates embryonic signaling to the oviduct as well as pregnancy-associated thrombocytopenia.

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“…Tryptase, a neutral protease stored in the cytoplasmic granules of all human mast cells, 24,32,38 can be released from human mast cells 24,31 and is a potent mitogen for human fibroblasts. 39 The tryptase content of heart tissue from patients with DCM (32.3Ϯ5.9 g/g wet tissue) and ICM (33.7Ϯ4.3 g/g wet tissue) was higher than that of control subjects (6.9Ϯ2.1 g/g wet tissue) (PϽ.05).…”

Section: Tryptase Content In the Failing Heartmentioning

confidence: 99%

Stem Cell Factor in Mast Cells and Increased Mast Cell Density in Idiopathic and Ischemic Cardiomyopathy

et al. 1998

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Background-We compared cardiac mast cell (HHMC) density and the immunological and nonimmunological release of mediators from mast cells isolated from heart tissue of patients with idiopathic dilated (DCM) (nϭ24) and ischemic cardiomyopathy (ICM) (nϭ10) undergoing heart transplantation and from control subjects (nϭ10) without cardiovascular disease. Methods and Results-HHMC density in DCM (18.4Ϯ1.6 cells/mm 2 ) and ICM (18.4Ϯ1.5 cells/mm 2 ) was higher than that in control hearts (5.3Ϯ0.7 cells/mm 2 ; PϽ.01). The histamine and tryptase contents of DCM and ICM hearts were higher than those of control hearts. The histamine content of the hearts was correlated with mast cell density (r s ϭ.91; PϽ.001). Protein A/gold staining of heart tissue revealed stem cell factor (SCF), the principal growth, differentiating, and activating factor of human mast cells, in HHMC secretory granules. Histamine release from cardiac mast cells caused by immunological (anti-IgE and rhSCF) and nonimmunological stimuli (Ca 2ϩ ionophore A23187) was higher in patients with DCM and ICM compared with control subjects. Immunological activation of HHMC induced a significantly greater release of tryptase and LTC 4 in patients with DCM and ICM compared with control subjects. Conclusions-Histamine and tryptase content and mast cell density are higher in failing hearts than in control hearts. SCF, present in secretory granules of HHMC, might represent an autocrine factor sustaining mast cell hyperplasia in heart tissue in these patients. The increased local release of fibrogenic factors (eg, histamine, tryptase, and leukotriene C 4 ) might contribute to collagen accumulation in the hearts of patients with cardiomyopathy. 1 Mast cells are present in human heart tissue 2,3 and in adventia and intima of coronary arteries of patients with coronary artery disease. [4][5][6] Moreover, the in vitro immunological activation of human heart tissue with anti-IgE induces the release of histamine and prostaglandin D 2 . 7,8 The concentration of histamine and the density of mast cells are increased in the arteries of cardiac patients, 4,5,9 and coronary arteries from cardiac patients are hyperresponsive in vitro to histamine. 4 Furthermore, in vivo administration of histamine and other mast cell-derived mediators (peptide LTC 4 ) in humans causes significant cardiovascular effects. 10 -12 Finally, serum IgE levels are increased in patients with coronary artery disease. 13,14 Taken together, these observations raise the possibility that local activation of cardiac mast cells might contribute, through the release of vasoactive mediators, to certain cardiovascular diseases. 15,16 Fibrosis is a hallmark of failing hearts in DCM and ICM. 17 The cells and the mediators responsible for fibroblast proliferation and collagen accumulation in failing hearts in DCM and ICM are largely unknown. Mast cells are involved in many types of inflammation and repair processes and are found in increased numbers in fibrotic tissues. For example, increased mast cell density has be...

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Inhibition by REV-5901 of leukotriene release from guinea-pig and human lung tissue in vitro

Cited by 19 publications

References 34 publications

Role of peptidoleukotrienes in capsaicin‐sensitive sensory fibre‐mediated responses in guinea‐pig airways.

Role of peptidoleukotrienes in capsaicin‐sensitive sensory fibre‐mediated responses in guinea‐pig airways.

Possible Role of Platelet-Activating Factor in Embryonic Signaling during Oviductal Transport in the Hamster1

Stem Cell Factor in Mast Cells and Increased Mast Cell Density in Idiopathic and Ischemic Cardiomyopathy

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