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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 779-784 
    ISSN: 1432-1912
    Keywords: 2-Chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) ; Hind-paw edema ; Vascular permeability ; Plasma exudation ; Passive cutaneous anaphylaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2-Chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) produced a dose-dependent inhibition of the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. A comparable inhibitory profile was observed in mice to which PP1D1 was injected i.p. or applied orally. Unlike dexamethasone, PP1D1 had no effect on the liver glycogen content in fasting adrenalectomized mice. Ear edema caused by passive cutaneous anaphylactic reaction, or by subcutaneous injection of compound 48/80, histamine, serotonin, bradykinin or substance P was reduced by PP1D1 in a dose-dependent manner. In addition, topical application of PP1D1 suppressed the capsaicin- and arachidonic acid-induced ear edema. In compound 48/80-pretreated mice, the tissue histamine content was greatly reduced. Under these conditions, PP1D1 reduced the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine plus methysergide. These results suggest that the inhibitory effect of PP1D1 on the edematous response is due to the protection of the microvasculature from mediator challenge.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 599-605 
    ISSN: 1432-1912
    Keywords: Key words Neutrophil (rat) ; Ca2+ influx ; U-73122 ; Phospholipase C inhibition ; U-73343 ; Cytosolic Ca2+ concentration ; Mn2+-quench
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  1-[6-[[17β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) has been proven to be a useful tool in investigation of phospholipase C (PLC)-coupled signal transduction during cell activation. In the present studies, the inhibition by U-73122 of cytosolic free Ca2+ concentration ([Ca2+]i) of neutrophils was investigated. U-73122 suppressed the [Ca2+]i elevation of neutrophils suspended in Ca2+-containing medium challenged by N-formyl-Met-Leu-Phe (fMLP), cyclopiazonic acid (CPA) and ionomycin. The concentrations of U-73122 required for inhibition of CPA- and ionomycin-induced changes with IC50 values 4.06±0.27 μM and 4.04± 0.44 μM, respectively, is almost 10-times that required for inhibition of the fMLP-induced response (IC50 value 0.62±0.04 μM). U-73122 also reduced the intracellular Ca2+ mobilization of neutrophils suspended in Ca2+-free medium stimulated by fMLP and CPA, but not by ionomycin, with IC50 values 0.52±0.02 μM and 6.82±0.74 μM, respectively. 1-[6-[[17β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-2,5-pyrrolidinedione (U-73343), a close analog of U-73122 that does not inhibit PLC activity, suppressed the [Ca2+]i elevation of neutrophils challenged by fMLP in Ca2+-containing medium, but not in Ca2+-free medium, with IC50 value 22.30±1.61 μM. In Mn2+-quench studies, U-73122 suppressed the Mn2+ influx in CPA-activated neutrophils (IC50 value was 7.16±0.28 μM) as well as in resting neutrophils (IC50 value was 6.72±0.30 μM). U-73343 also suppressed the Mn2+ influx in resting neutrophils in a concentration-dependent manner. These results suggest that the inhibitory effect of U-73122 on [Ca2+]i of activated neutrophils is attributed partly to the suppression of Ca2+ release from the intracellular Ca2+ stores through PLC inhibition, and partly to the blockade, especially at higher concentrations, of Ca2+ entry from the extracellular space through PLC-independent processes.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 353 (1996), S. 599-605 
    ISSN: 1432-1912
    Keywords: Neutrophil (rat) ; Ca2+ influx ; U-73122 ; Phospholipase C inhibition ; U-73343 ; Cytosolic Ca2+ concentration ; Mn2+-quench
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 1-[6-[[17a-3-Methoxyestra-1,3,5(10)-trien17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) has been proven to be a useful tool in investigation of phospholipase C (PLC)-coupled signal transduction during cell activation. In the present studies, the inhibition by U-73122 of cytosolic free Ca2+ concentration ([Ca 2+]i) of neutrophils was investigated. U-73122 suppressed the [Ca2+]i elevation of neutrophils suspended in Ca2+-containing medium challenged by N-formyl-Met-Leu-Phe (fMLP), cyclopiazonic acid (CPA) and ionomycin. The concentrations of U-73122 required for inhibition of CPA- and ionomycin-induced changes with IC50 values 4.06 ± 0.27 µM and 4.04 ± 0.44 µM, respectively, is almost 10-times that required for inhibition of the fMLP-induced response (IC50 value 0.62 ± 0.04 µM) U-73122 also reduced the intracellular Ca2+ mobilization of neutrophils suspended in Ca 2+-free medium stimulated by fMLP and CPA, but not by ionomycin, with IC50 values 0.52 ± 0.02 µM and 6.82 ± 0.74 µM, respectively. 1-[6-[[17f3-Methoxyestra-1,3,5(10)-trien-l7-yl]amino]hexyl]2,5-pyrrolidinedione (U-73343), a close analog of U-73122 that does not inhibit PLC activity, suppressed the [Ca2+]i elevation of neutrophils challenged by fMLP in Ca2+-containing medium, but not in Ca2+-free medium, with IC50 value 22.30 ± 1.61 µM. In Mn2+-quench studies, U-73122 suppressed the Mn2+ influx in CPA-activated neutrophils (IC50 value was 7.16 ± 0.28 µM) as well as in resting neutrophils (IC50 value was 6.72 ± 0.30 μM). U-73343 also suppressed the Mn2+ influx in resting neutrophils in a concentration-dependent manner. These results suggest that the inhibitory effect of U-73122 on [Ca2+]i of activated neutrophils is attributed partly to the suppression of Ca2+ release from the intracellular Ca2+ stores through PLC inhibition, and partly to the blockade, especially at higher concentrations, of Ca2+ entry from the extracellular space through PLC-independent processes.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 354 (1996), S. 779-784 
    ISSN: 1432-1912
    Keywords: Key words 2-Chloro-3-methoxycarbonylpropionamido-1 ; 4-naphthoquinone (PP1D1) ; Hind-paw edema ; Vascular permeability ; Plasma exudation ; Passive ; cutaneous anaphylaxis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract 2-Chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D1) produced a dose-dependent inhibition of the polymyxin B-induced hind-paw edema in normal as well as in adrenalectomized mice. A comparable inhibitory profile was observed in mice to which PP1D1 was injected i.p. or applied orally. Unlike dexamethasone, PP1D1 had no effect on the liver glycogen content in fasting adrenalectomized mice. Ear edema caused by passive cutaneous anaphylactic reaction, or by subcutaneous injection of compound 48/80, histamine, serotonin, bradykinin or substance P was reduced by PP1D1 in a dose-dependent manner. In addition, topical application of PP1D1 suppressed the capsaicin- and arachidonic acid-induced ear edema. In compound 48/80-pretreated mice, the tissue histamine content was greatly reduced. Under these conditions, PP1D1 reduced the bradykinin- and substance P-induced ear edema to a significantly greater extent than diphenhydramine plus methysergide. These results suggest that the inhibitory effect of PP1D1 on the edematous response is due to the protection of the microvasculature from mediator challenge.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
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