ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb03316.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Histamine release from isolated rat mast cells induced by extracellular adenosine 5′‐triphosphate (ATP) in the presence of calcium was preceded by the uptake of sodium and45Ca in the cells. In contrast, the release induced by compound 48/80, n‐decylamine and chlorpromazine was not preceded by uptake of45Ca. Histamine release and45Ca uptake by ATP were completely inhibited byp‐hydroxymercuribenzoate and incubation at 0°, whereas sodium uptake was partly reduced. In the presence of 2.5 mM‐CaCl2, ATP activated the uptake of45Ca whereas, as previously reported, no sodium uptake or histamine release occurred. All three effects of ATP were inhibited by MgCl2. Thus, under conditions where the uptake of either sodium or45Ca was inhibited, no histamine release was induced by extracellular ATP.Antimycin A did not inhibit ATP‐induced increase in membrane permeability for sodium and calcium but completely blocked the histamine release. It is concluded that for histamine release to be induced by extracellular ATP from rat mast cells, an increased cell membrane permeability for sodium and calcium is necessary but not in itself sufficient since the release reaction is also dependent on the metabolic state

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

In order to prevent the reabsorption of biliary excreted mercury in methyl mercuric chloride exposed mice, the animals were treated with a macro‐molecular polythiol (mercaptodextran) synthesized by thiolating a dextran compound using N‐acetylhomocysteine thiolactone. The polythiol given in the food at a concentration of 5 % reduced the average biological half time of mercury from 11.6 days to 5.9 days. Mercury levels in blood, liver and kidney were reduced to about 50 % after 10 days as compared to control animals, and the brain level was reduced to about 70 %. Faecal excretion of mercury compounds was not changed during 10 days, but the urinary excretion increased by a factor of 5. The effect of the macromolecule seems to be related to N‐acetylhomocysteine in that it is released in the gastrointestinal tract, and this compound given alone has the same effect as the macromolecule. Corresponding results can be obtained by the intravenous injection of N‐acetylhomocysteine. This indicates that the mechanism includes the formation in the gastrointestinal tract or in the blood of a N‐acetylhomocysteine‐methyl‐mercuric complex. This complex is easily absorbed when formed in the gastrointestinal tract, and it is easily excreted

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The effect of chlorhexidine (Chx) on some biochemical parameters of rat liver microsomes was studied. At concentrations of Chx above 100 μM a precipitate was formed with the microsomes and the precipitate was maximal above 200 μM. The major part of the microsomal proteins was also precipitated at concentrations of Chx exceeding 200 μM. When the concentration of Chx was higher than 75 μM cytochrome P‐450 was partly precipitated and partly converted to cytochrome P‐420. A concentration dependent inhibition ofp‐nitro‐anisole‐O‐demethylase was observed, the activity being almost totally inhibited at 600 μM. The activity of microsomal glucose‐6‐phosphatase was markedly enhanced (70‐80 %) by Chx at concentrations above 75 μM although the activity of the enzyme was precipitated by Chx. The microsomes bound increasing amounts of Chx with increasing concentrations of the compound until about 1000 μM at which concentration

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

Chlorpromazine (CPZ) 1.5 × 10‐4M inhibits the uptake of hypoxanthine into the acid‐soluble fraction of human skin epithelial cells (NCTC 2544) grown in culture to 42 % of the controls, whereas the uptake of adenine is only reduced to 85 % of the controls. The cellular uptake of guanine is virtually absent. CPZ does not change the activity of hypoxanthine, adenine or guanine phosphor‐ribosyltransferases in homogenates of the cells. Excess adenine inhibits the cellular uptake of hypoxanthine, whereas excess hypoxanthine does not alter the uptake of a

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

A modification of the Hajdu&Häussler method (1964) for the determination of furosemide is described. The sensitivity is 10±2 ng/ml. The binding of furosemide to plasma proteins is determinedin vitroat room temperature by an ultrafiltration method. At concentrations between 10 and 400 μg/ml, 99‐95% was bound in normal plasma. In therapeutically dialysed plasma from surgical patients with acute renal failure the binding was reduced by 9‐14%. The number of μg of drug bound per mg albumin was also significantly reduced in the patient plasma. A “Kav1value” for the range 10‐100 μg/ml was approximately 3 × 105in donor plasma and 2 × 104in patient plasma. A “kav2value” (100‐400 μg/ml) was 3 × 104in donors and 8 × 103in patients. The kav1and kav2values were significantly lower in patient plasma than in donor plasma and also lower in patient plasma than in Ringer solutions to whi

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00724.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The uptake of14C‐neostigmine in striated muscles was studied after intravenous injection into rats and in the isolated rat diaphragm. 120 minutes after the intravenous injection of14C‐neostigmine (100 μg/kg) the14C‐concentration in the quadriceps, sternomastoid and intercostal muscles was 1/3‐1/2 of the concentration in the plasma, whereas the14C‐concentration in the diaphragm was about double the concentration in the plasma. After continuous intravenous infusion of14C‐neostigmine the distribution pattern was the same as after a single injection. Paper chromatography showed that the radioactivity in the diaphragm was due partly to unchanged neostigmine, partly to a metabolite. In the isolated diaphragm unchanced14C‐neostigmine accumulates against an apparant concentration gradient. The uptake is partly saturable and energy‐dependent. It is suggested that intracellular accumulation of neostigmine and/or its metabolites may be causally related to the respiratory failure following overdosag

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00725.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

The treatment of hepatic microsomes with phospholipase A or phospholipase C decreased the drug hydroxylase activity. The exception was the aryl hydrocarbon hydroxylase in hepatic microsomes from 3‐methylcholanthrene pre‐treated rats. Its specific activity remained unchanged after phospholipase A digestion. In hepatic microsomes from phenobarbital pretreated rats the aryl hydrocarbon hydroxylase was not significantly increased and after phospholipase A or phospholipase C digestion, it decreased in both treated and control rats. The phenobarbital or 3‐methylcholanthrene inducedp‐nitroanisole 0‐demethylase activity in liver microsomes decreased in a manner corresponding to the decrease in cytochrome P‐450 (P‐448) concentrations. The treatment of hepatic microsomes with phospholipase A or phospholipase C activated the membrane‐bound UDP glucuronosyltransferase both in control and drug‐treated rats. Phospholipase A increased the measurable UDP glucuronosyltransferase activity particularly in hepatic microsomes from 3‐methylcholanthrene pretreated rats. However, digestion with trypsin was necessary in order to detect the induction in UDP glucuronosyltransferase after phenobarbital pretreatment of rats. Other agents studied, such as phospholipase A or C, digitonin, cetylpyridinium chloride, or NaSCN, were unable to do this. Digestion with trypsin released considerable amounts of UDP glucuronosyltransferase activity into 27,000 g supernatant, especially from phenobarbital microsomes, whereas phospholipase A was more active in releasing UDP glucuronosyltransferase into 27,000 g supernatant from hepatic microsomes of 3‐methylcholanthrene pretreated rats. Membrane perturbating agents seem to differ in their action towards the hepatic microsomal membranes obtained from rats treated with phenobarbital or

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00726.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY

摘要:

KWD 2058 is the diisobutyric acid ester of terbutaline (bricanyl®), a β2‐re‐ceptor selective sympathomimetic bronchodilator. KWD 2058 relaxed isolated bronchial smooth muscle obtained from the guinea‐pig, cat and man, but in isolated cat bronchial preparations pre‐treated with the esterase inhibitor eserine, KWD 2058 was inactive in concentrations that relaxed the normal preparations (ED50: 0.2 μg/ml). This indicates that the effect of KWD 2058 is due to the formation of terbutaline and not to the unchanged diester. KWD 2058 had no effects on isolated guinea‐pig auricle preparations (up to 2 ug/ml) or on isolated guinea‐pig hearts (up to 10 μg). In isolated cat hearts, KWD 2058 increased the frequency but lacked positive inotropic effects. In anaesthetized cats, KWD 2058 and terbutaline were equipotent on a molar basis as to the inhibitory effects following respiratory overflow. On cardiovascular parameters KWD 2058 was somewhat less potent than terbutaline, whereas the effect on the soleus muscle of the two compounds did not differ significantly. KWD 2058, given subcutaneously and orally, protected unanaesthetized guinea‐pigs against histamine aerosol. Administered orally, KWD 2058 was 6 times more active than terbutaline. KWD 2058 given in bronchodilating doses did not affect the barbiturate sleeping time or the locomotor activity in mice. The LD50 for KWD 2058 in mice was 52 mg/kg intravenously, 450 mg/kg subcutaneously, 270 mg/kg intraperitoneally and 1750 mg/kg given orally. It is concluded that KWD 2058 is hydrolyzed to terbutaline, which is the active agent responsible for the β2‐receptor stimulating effect seen after administration of KWD 2058. The esterification of terbutaline has resulted in a significantly improved oral potency in guinea‐pigs and a tendency to less cardiovascular effects in relation to the

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1974.tb00727.x

出版商:Blackwell Publishing Ltd    

年代:1974

数据来源: WILEY