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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Clinical and experimental pharmacology and physiology 15 (1988), S. 0 
    ISSN: 1440-1681
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: b1. The inhibition of α-tocopherol and calmodulin-stimulated phosphodiesterase activities was investigated in vitro.2. Anthracyclines—doxorubicin, daunorubicin and aclacinomycin—inhibited calcium calmodulin-stimulated cyclic 3′,5′-AMP (cAMP) nucleotide phosphodiesterase (EC. 3.1.4–17) activity (IC50= 33.00 ± 3.50–36.50 ± 2.75 μmol/l). The stimulation of this enzyme by α-tocopherol was also inhibited by doxorubicin (IC50= 18.50 ± 4.00 μmol/l).3. The anthracycline-induced inhibition of the calcium calmodulin and α-tocopherol-stimulated phosphodiesterase activity was competitive with calmodulin and α-tocopherol respectively. Increasing the concentration of the substrate, cAMP or calcium ions did not attenuate the drug-induced inhibition. The basal activity of the enzyme was not inhibited by concentration of doxorubicin up to 50 μmol/l.4. In vivo, single dose drug distribution studies of the fluorescence of doxorubicin indicate that in the heart after a cardiotoxic dose (20 mg/kg), myocardial concentrations were achieved which could cause 70–80% inhibition of this phosphodiesterase enzyme.5. Inhibition of calmodulin function by anthracyclines via direct interaction with calmodulin may contribute significantly to the effects of anthracyclines, such as disturbance in calcium homeostasis as well as acute and chronic deleterious effects on the myocardium. The action of α-tocopherol to bind or complex anthracycline may in part contribute to its protection against anthracycline-induced membrane damage and cardiotoxicity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 16 (1986), S. 133-138 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The hydrophobic probes anthroylcholine ((AC), 8-anilino-1-napthalene sulfonate (ANSE), and 2-P-toluidinyl naphthalene 6-sulfonate (TNS) increased calcium-calmodulin (Ca2+−CaM) fluorescence. This fluorescence was decreased by doxorubicin (DXR) in a dose-dependent fashion. The Ca2+ ion was an absolute requirement for the observed effects of DXR. DXR bound to the Ca2+−CaM complex (Kd=4.2×10-5 M, Bmax=1.8) and to alpha tocopherol. The binding of untransformed (native) DXR to CaM was a reversible process. These data support a previous finding that DXR inhibits stimulation of calmodulin-deficient PDE (a CaM target enzyme) using either the Ca2+ CaM complex or alpha tocophenol by interacting with these agents, and suggest that other target enzymes for CaM may be similarly affected.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 205 (1983), S. 251-262 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Many reports have indicated that estrogens increase uterine guanosine 3′,5′-cyclic monophosphate (cGMP)levels via increasing the activity of guanylate cyclase. In the present study, guanylate cyclase activity was studied cytochemically in the oviduct of immature rats 24 hours after one or two doses (20 μg/kg, subcutaneously) of diethylstilbestrol (DES), one dose per day. The reaction product indicating guanylate cyclase was localized in the plasma membrane of epithelial cells, endothelial cells, and smooth muscle cells of all DES-treated animals, but was absent from those of the vehicle control immature rats. The Golgi saccules of secretory cells and the periciliary membrane of ciliated cells were stained for the enzyme 24 hours after the first and second dose of DES, but the activity seemed diminished 24 hours after the second dose. Likewise, reaction product indicating guanylate cyclase was more prominent in the plasma membrane of epithelial cells of animals treated with one dose of DES than those animals treated with two doses of DES. However, in the endothelial and smooth muscle cells, guanylate cyclase activity increased after two doses of the estrogen. Further, pinocytotic vesicles or caeolae in these cells were also strongly stained for the enzyme after one and two doses of DES. These findings confirm the suggestion that guanylate cyclase plays a significant role in the growth, differentiation, and function (secretion and transport) of the oviduct.
    Additional Material: 14 Ill.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Journal of Morphology 171 (1982), S. 1-10 
    ISSN: 0362-2525
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The effect of ovarian hormones on the activities of glucose-6-phosphatase and alkaline phosphatase in the vaginal epithelium was studied in immature and ovariectomized rats, using ultracytochemical techniques. Comparative studies were done on normal rats at the luteal phase and on day 14 of pregnancy.Various vaginal cells show different degrees of response to progesterone and diethylstilbestrol (DES) with regard to glucose-6-phosphatase activity. Intense glucose-6-phosphatase activity was observed in the cisternae of granular endoplasmic reticulum (rER), Golgi saccules and vesicles, and nuclear envelope of both basal cells and stromal cells of progesterone treated rats, whereas in the basal cells and stromal cells of DES-treated and control animals the enzyme was totally lacking. Detectable glucose-6-phosphatase activity was also observed, however, in the rER cisternae and Golgic complex of keratohyalin-secreting squamous intermediate cells of the vaginal epithelium of DES-treated rats. Alkaline phosphatase was observed in the plasma membranes of various cell types of vaginal epithelium in the normal, progesterone-, and DES-treated rats, Alkaline phosphatase was also found on the limiting membranes of secretory granules of mucocytes in animals at the luteal phase and during pregnancy. DES and progesterone in the doses used did not affect alkaline phosphatase activity in the rat vagina. Overall, progesterone enhances glucose-6-phosphatase activity in basal cells of the rat vagina prior to completion of mucification. Alkaline phosphatase was found in all cells involved in mucin secretion.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
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