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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The mechanism of involvement of monoamine oxidase (MAO) in catecholamine-stimulated prostaglandin (PG) biosynthesis was studied in the particulate fraction of rat brain homogenates. High concentrations of either noradrenaline (NA) or dopamine (DA) stimulated effectively PGF2α formation. The same amount of 2-phenylethylamine (PEA) acted similarly, provided that it was administered together with a catecholamine analogue or metabolite possessing the 3,4-dihydroxyphenyl nucleus–3, 4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenyl-glycol (DOPEG), 3,4-dihydroxyphenylacetaldehyde (DOPAL), or α-methylnoradrenaline (α-met-NA)–or with SnCl2. In the absence of PEA, these compounds were ineffective with regard to stimulation of PGF2α formation. Catalase, pargyline, or indomethacin abolished completely PGF2α formation elicited either by catecholamines or by PEA plus a 3,4-dihydroxyphenyl compound or SnCl2. With regard to the stimulation of PGF2α formation in the presence of α-met-NA, PEA could be replaced by H2O2, generated by the glucose oxidase(GOD)-glucose system. The effect of H2O2 was inhibited by indomethacin or catalase, but pargyline was ineffective. It is assumed that catecholamines play a dual role in the activation of PG biosynthesis in brain tissue. During the enzymatic decomposition of catecholamines MAO produces H2O2, which stimulates endoperoxide synthesis. Simultaneously, catecholamines as hydrogen donors promote the nonenzymatic transformation of endoperoxides into PGF2α. The possible physiological importance of these findings is discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Doxorubicin-resistant Friend erythroleukemia cells, line F4–6 ADM2R, were selected by exposure of wild-type F4-6 cells to doxorubicin concentrations of up to 1 μg/ml. In these cells, increased expression of multidrug resistance (MDR) genes was demonstrated by Northern blot analysis. The growth-inhibitory effect of doxorubicin, daunorubicin,N,N-dimethyldoxorubicin,N,N-dimethyldaunorubicin, morpholinodoxorubicin, and pyrromycin was comparatively investigated in resistant and wild-type cells. The doxorubicin-resistant F4-6 cells showed approx. 200-fold resistance to doxorubicin and about 100-fold resistance to daunorubicin with respect to the drug-sensitive counterpart. A dramatic decrease in resistance was observed for theN,N-dimethylated derivatives of doxorubicin and daunorubicin as well as for theN,N-dimethylated natural anthracycline pyrromycin and for morpholinodoxorubicin. Uptake studies using [14C]-daunorubicin and [14C]-N,N-dimethyldaunorubicin in resistant F4-6 cells showed a decreased accumulation of daunorubicin but no significant reduction inN,N-dimethyldaunorubicin accumulation as compared with the wild-type cells. Treatment with verapamil led to increased intracellular levels of daunorubicin in resistant cells, whereas an excess ofN,N-dimethyldaunorubicin did not have this effect. Thus, the decreased resistance of the doxorubicin-resistant F4-6 cells to theN-alkylated anthracyclines may at least in part be due to a reduced affinity of these compounds for the efflux pump. The results indicate that the dimethylation of the amino group of the anthracycline sugar moiety and its incorporation within a morpholinyl ring may overcome MDR by similar mechanisms.
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  • 3
    ISSN: 1573-4935
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Treatment of Friend-erythroleukemia cells with 1.5% dimethylsulfoxide (DMSO) caused a decrease in ouabain sensitive 86Rb+-uptake beginning six to seven hours after DMSO addition indicating a reduced function of the Na+, K+-pump. However, analysis of the ouabain sensitive 86Rb+-uptake after Na+-preloading of the cells as well as measurements on the Na+, K+-ATPase activity in isolated membrane fragments revealed that no inhibition of the Na+, K+-ATPase occurred during the first 12 hours. On the contrary the Na+, K+-ATPase activity was initially enhanced and then returned to control levels during the early phase of induction by DMSO. On the other hand, 22Na+-transport into DMSO-treated cells was reduced similar to the ouabain sensitive 86Rb+ uptake in cells without Na+ preloading. The piretanide sensitive 86Rb+-uptake, due to the Na+, K+, 2Cl- cotransport system was inhibited after seven hours exposure to DMSO. Some three hours after DMSO addition the incorporation of 35S-methionine into proteins began to decrease, which was accompanied with or followed by a reduction in the methionine uptake of DMSO treated cells. Membrane-potential-dependent tetraphenylphos-phonium cation uptake was not altered relative to the controls in the first 12 hours following DMSO addition. These results suggest that the reduced activity of the Na+, K+-pump in Friend cells after DMSO exposure is not due to inhibition of the Na+, K+-ATPase, but most probably due to a smaller Na+-influx, which results from inhibition of Na+-cotransport processes (amino acid uptake, Na+, K+, 2Cl- cotransport system).
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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