摘要:

AbstractThe effect of prolonged digoxin treatment (1 mg/kg day for 8 days) on the activity levels of some enzymes of energy metabolism (phosphofructokinase, lactate dehydrogenase, citrate synthase, succinate dehydrogenase) in rat myocardium was studied. In the control animals receiving the solvent mixture (glycerol: ethanol:water in 1:1:1) a transient decrease in the lactate dehydrogenase and citrate synthase activity levels was observed. In the hearts of digoxin treated rats the level of activity of phosphofructokinase was permanently lowered by the fourth day and the level of activity of citrate synthase permanently increased after the first day of treatment. A transient increase in the activity level of succinate dehydrogenase in the myocardium of digoxin treated animals was seen between days 1 and 6. In this study a permanent decrease in phosphofructokinase and an increase in citrate synthase activity levels in rat heart muscle was noted during prolonged digoxin treatment.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02164.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractSamples from 44 arctic foxes (Alopex lagopus), caught near Longyearbyen on Svalbard, were analyzed with respect to their content of PCB. Gas chromatographic‐mass spectrometric investigations revealed that 7 PCB components constituted the main part of the total PCB present. These components were quantified individually. A moderate degree of PCB contamination was recorded. Calculated on a fat weight basis, the total concentrations of PCB in fat tissue and liver were about equal, but the relative amounts of most of the PCB components present were different in the 2 tissues. The total amount of PCB in brain, calculated on a fat weight basis, was significantly less than the corresponding concentrations in liver, kidney, muscle, and fat tissue. The special distribution trend observed in this study is related to the structure of the PCB components present and the arctic nature of the sampling are

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02165.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractIsolated ring preparations of human vein were contracted by potassium (127 mM) and noradrenaline (1.8 × 10‐5M). The potassium‐induced contracture developed more rapidly and had a higher maximum amplitude than that produced by noradrenaline. Addition of phentolamine (10‐5M) reduced the amplitude of the potassium contracture by 22% and abolished the noradrenaline response. Verapamil and nitroglycerin relaxed preparations contracted by potassium and noradrenaline, and, when added prior to stimulation, reduced the contractile responses to these agents. Both verapamil and nitroglycerin inhibited the contractile effect of noradrenaline more strongly than that of potassium. After immersion of the preparations for 30 min. in a calcium‐free medium, the responses to potassium and noradrenaline were reduced to 21.3 ± 2.5% and 7.1 ±0.8%, respectively, of the control. Addition of verapamil caused a further reduction of the response to potassium, but not of that to noradrenaline. Nitroglycerin caused a further reduction of the contractions induced by both agents. When the calcium concentration in the extracellular medium was increased from 0 to 4 mM, the contractile responses to potassium and noradrenaline returned to the control level. Both verapamil and nitroglycerin inhibited the contractile responses to calcium; the inhibiting effects of verapamil were significantly more marked than those of nitroglycerin. Tachyphylaxis to nitroglycerin was demonstrated on contractions induced by potassium, but not on noradrenaline‐produc

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02166.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractPurified phospholipase C (phosphatidylcholine cholinephosphohydrolase, EC 3.1.4.3) and thetatoxin fromClostridium perfringensboth inhibited noradrenaline‐stimulated lipolysis and cyclic AMP accumulation in isolated rat adipocytes in a dose‐dependent manner. The action of phospholipase C was gradual in onset, while the effect of theta‐toxin was almost immediate. Phospholipase C., but not theta‐toxin, hydrolyzed membrane phospholipids and inhibited adenylate cyclase (EC 4.6.1.1) in a crude membrane fraction from fat cells. The inhibitory effects of phospholipase C were associated with morphological alterations detectable by electron microscopy, whereas effects of theta‐toxin were observed at a time when no clearcut morphological alterations could be observed. It is concluded that the two purified principles fromC. perfringens, which are both present in commercial preparations of phospholipase C., antagonize noradrenaline‐stimulated cyclic AMP accumulation and lipolysis. Although their exact mechanisms of action have not been elucidated, phospholipase C and theta‐toxin have different mo

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02167.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractUsing a single column of a strongly acidic cation exchange resin (Dowex 50W, X‐4, 200–400 mesh, resin bed 4.0 mm diameter × 75 mm long in sodium form), noradrenaline (NA) (together with adrenaline (A)), dopamine (DA), 5‐hydroxytryptamine (5‐HT), and histamine (Hm), are recovered in separate eluates after a single extraction of the same tissue sample into perchloric acid. Recoveries of the amines from homogenates and filtrates were approximately the same: for NA (together with A), about 90% in a 7‐ml eluate; for DA, about 95% in 3.5 ml; for 5‐HT, about 75% in 7 ml; and for Hm, about 85% in 4.5 ml. The establishment and routine use of the procedure are presented in detail. Several metabolites of the amines, including 5‐hydroxyindole‐3‐acetic acid (5‐HIAA), the precursor amino acids, and 3‐methoxytyramine (3‐MT), can be recovered from the same Dowex 50 column by incorporating the procedures developed by Carlsson, Kehr&Lindqvist in this laboratory. All the amines and many of their metabolites can be purified successively into their eluates in a normal working day. We now have increased opportunities to study aspects of the metabolism of the biogenic amines. Thus, for the catecholamines can be monitored tyrosine → DOPA → DA → NA → A and also DA → 3‐MT; and for 5‐HT, the metabolic pathway tryptophan 5‐hydroxytryptophan → 5‐HT → 5‐HIAA. The column purification contributes considerable specificity to the overall procedure. Most compounds which are acidic; e.g. 5‐HIAA, neutral or amphoteric, e.g. all the precursor amino acids, are eluted before the amines. Considerable resolution of basic compounds into separate fractions is also achieved: notably Hm is eluted before spermidine, and DA is separated from NA plus A. Thus, many compounds are prevented from interfering in fluorimetric assays which have been especially adapted for measuring these amines in the Dowex 50 eluates. Salt equivalent to at least 10 g of tissue placed on the column does not affect the recoveries of the amines. For quantitative determinations of endogenous amines, approximately 10 ng of each amine on the Dowex 50 column are sufficient, and smaller amounts can be detected. The procedure was developed particularly for measuring amines in nervous tissue, but it has been applied successf

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02168.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractFive healthy volunteers received single doses of imipramine‐N‐oxide (1 mg/kg) by the oral, intramuscular, and intravenous routes. Peak plasma level of imipramine‐N‐oxide was reached one hour after oral administration. The plasma curves of imipramine‐N‐oxide following oral and intravenous administration suggested a monophasic decay with a half‐life ranging between 1.5–2.5 hrs. Pronounced individual differences were observed in the plasma and blood cell concentrations of imipramine‐N‐oxide and the formed metabolites, imipramine and desipramine. The systemic availability of the oral dose of imipramine‐N‐oxide averaged 100 per cent, whereas the systemic availability of the intramuscular injection of imipramine‐N‐oxide averaged 54 per cent. The formation of metabolites was more extensive after intramuscular injection compared with the other routes of administration. The concentration of imipramine‐N‐oxide was lower and the imipramine concentrations higher in blood cells compared to the plasma after all three routes of administration. Thirteen depressed patients received continuous treatment with weekly increasing oral doses of imipramine‐N‐oxide for three weeks and intramuscular injections during the fourth week. They received imipramine during the fifth week. The concentration of imipramine‐N‐oxide and the formed imipramine and desipramine were determined every week both in the plasma and blood cells. The concentration of imipramine and desipramine was lower during treatment with imipramine‐N‐oxide than during treatment with the same dose of imipramine in samples taken 12 hrs after the last dose. In spite of the low concentrations a good clinical effect was noted in the patients investigated. There is a possibility of extensive intracellular formation of imipramine as indicated by the high content of imipramine in the blood cells during the first hours aft

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02169.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractRats were given imipramine‐N‐oxide as single intramuscular injection and then as repeated oral doses. Imipramine‐N‐oxide and the metabolites imipramine and desipramine were analysed in the blood cells, plasma and brain tissue. The concentration of imipramine‐N‐oxide increased simultaneously in the brain and blood, reaching a peak 45 minutes after a single dose. Imipramine was the quantitatively predominant metabolite in the blood cells and brain, while desipramine reached a higher concentration than imipramine in the plasma. Samples taken at different times after oral doses during continuous treatment showed fairly constant concentrations of imipramine‐N‐oxide and desipramine in the brain, whereas the concentration of imipramine was m

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02170.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractNeuroleptics from various chemical groups and some amino acids were examined for GABA uptake‐inhibiting properties in rat brain synaptosomes. The phenothiazine and thioxanthene neuroleptics inhibited GABA uptake by 50% in the concentration range of 10–30 μM. No difference in potency was found between the cis and the trans isomers of the thioxanthenes. Clozapine and particularly sulpiride were weak inhibitors of the GABA uptake process, whereas some of the butyrophenones examined exhibited rather potent effect. Specific GABA uptake inhibitors (nipecotic acid and guvacine) were as active as the most potent butyrophenones. As no significant correlation was obtained between GABA uptake‐inhibiting effect of the neuroleptics and their clinical or pharmacological effects it is concluded that the influence on GABA uptake is not an important aspect of the neuroleptic

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02171.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY

摘要:

AbstractFolate in cow's milk was strongly bound to a minor whey protein. Methotrexate inhibited the folate binding in a log dosis dependent manner, but was a rather weak inhibitor. The binding mechanism of folate changed from a cooperative to a non‐cooperative type in the presence of methotrexate. This model system could be used in investigations on human body fluids and tissue

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1978.tb02172.x

出版商:Blackwell Publishing Ltd    

年代:1978

数据来源: WILEY