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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Molecular and cellular biochemistry 119 (1993), S. 185-193 
    ISSN: 1573-4919
    Keywords: heart sarcolemma ; adenylyl cyclase ; signal transduction ; alamethicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Alamethicin is commonly used as an agent for unmasking the latent enzyme activities in vesicular membrane preparations; however, relatively little is known about the effect of this agent on the characteristics of adenylyl cyclase in heart sarcolemma. By employing rat heart sarcolemmal preparation, we observed 5 to 6 fold increase in adenylyl cyclase activity upon treatment with alamethicin. Kinetic experiments using various concentrations of MgATP revealed that the increase in adenylyl cyclase activity in alamethicin treated membranes was associated with an increase in Vmax as well as affinity of the substrate for the enzyme. Dose-responses of the control and alamethicin-treated preparations to various activators of adenylyl cyclase revealed that the sensitivity of the enzyme to forskolin, NaF and GppNHp, was markedly increased upon treating sarcolemma with alamethicin. The activation of adenylyl cyclase by forskolin was also enhanced by increasing the concentration of alamethicin in the incubation medium. Furthermore, there was a greater increase in adenylyl cyclase activity with different concentrations of Mn2+ in the presence of alamethicin. These results suggest that alamethicin treatment alters the characteristics of adenylyl cyclase in addition to unmasking the enzyme activity in the purified sarcolemmal vesicular preparation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cardiovascular drugs and therapy 10 (1996), S. 231-238 
    ISSN: 1573-7241
    Keywords: catecholamine-induced cardiotoxicity ; cardiac Ca2+ transport ; oxidative stress ; cardiac membranes ; intracellular Ca2+ overload
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The occurrence of excessive catecholamine release is often associated with stress due to the lifestyle of Western societies. Contrary to the general thinking that excess catecholamines produce cardiotoxicity mainly via binding to adrenoceptors, there is increasing evidence that catecholamine-induced deleterious actions may also occur through oxidative mechanisms. In this overview it is shown that a high dose of isoproterenol induces a biphasic change in cardiac Ca2+ transport in the sarcolemma and in sarcoplasmic reticulum. Both sarcolemmal and sarcoplasmic reticular Ca2+-transport activities are initially increased to maintain Ca2+ homeostasis and then are impaired, which may be associated with the occurrence of intracellular Ca2+ overload. On the other hand, mitochondrial Ca2+-transport activities exhibited a delayed increase. Pretreatment with vitamin E partially prevented the deleterious changes in cardiac membranes as well as the depressed energetic status of the heart muscle cell. It is concluded that excess catecholamines affect Ca2+-transport mechanisms primarily via oxidation reactions involving free radical-mediated damage. Thus drug approaches that reduce circulating catecholamines and/or prevent their oxidation should prove beneficial. A combination therapy involving inhibitors of catecholamine release, blockers of adrenoceptors, and antioxidants may be indicated for stress-induced heart disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7241
    Keywords: plasma catecholamines ; heart catecholamine ; heart function ; diet restriction ; sympathetic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To examine the relationship between heart function and plasma catecholamines upon food restriction, normal adult rats were fed 12 g or 6 g food/day for 14 days and 12 g food/day for 28 days. Food-restricted rats exhibited bradycardia, hypotension, and decreased rates of cardiac contraction (+dP/dt) as well as relaxation (-dP/dt) at 14 (12 or 6 g food/day) and 28 (12 g food/day) days. Plasma norepinephrine and epinephrine levels were significantly elevated in the 6 g food/day group at 14 days, whereas in the 12 g food/day group, plasma norepinephrine was elevated at 14 days but was significantly decreased at 28 days. Heart norepinephrine and epinephrine concentrations were elevated at both 14 and 28 days of food restriction in the 12 g food/day group as well as at 14 days in the 6 g food/day group. Thus, dietary restriction appears to result in depressed indices of heart function, while the circulating levels of catecholamines were elevated at early states.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-4919
    Keywords: plasma adrenolutin ; adrenochrome ; catecholamines ; oxidation of catecholamines
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Using the reverse phase high-performance liquid chromatography (HPLC) with mobile phases composed of simple acids, we have developed an assay technique for the measurement of adrenolutin, one of the oxidation products of catecholamines, in rat plasma. Ion-pairing chromatography permits the separation and quantitation of plasma adrenolutin (μM) in a linear manner. Sample preparation involved the precipitation of plasma proteins with perchloric acid and it is easier to handle a large number of samples at a time. However, we were unable to demonstrate the presence of adrenochrome, another oxidation product of catecholamines, in plasma since adrenochrome was rapidly destroyed in acid as well as in blood and was quickly changed, into adrenolutin. Adrenolutin peak in HPLC was confirmed by 1) the retention time; 2) co-injection of adrenolutin and; 3) the appearance of 3H-adrenolutin after injection of 3H-norepinephrine. Administration of different catecholamines as well as adrenochrome and adrenolutin in rats also increased the level of adrenolutin in plasma. Adrenolutin was found to be present in plasma in other species including dog, rabbit and pig. High level of adrenolutin, which may represent total concentration of aminolutin in plasma, suggests the presence of an efficient mechanism for the oxidation of catecholamines under in vivo conditions.
    Type of Medium: Electronic Resource
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