摘要:

Abstract:The specificity of electrophoretically homogeneous preparations of rabbit liver microsomal cytochrome P‐450lm2–4towards oxygenation of n‐hexane, 7‐ethoxyresorufin and benzo(a)pyrene was examined using a reconstituted system consisting of cytochrome P‐450, NADPH‐cytochrome P‐450 reductase and dilauroylphosphatidylcholine. Epoxide hydrase was included when benzo(a)pyrene was used as substrate. Cytochrome P‐450lm2was most active in n‐hexane and benzo(a)pyrene oxygenation especially with regard to the formation of 2‐hexanol, B(a)P‐4,5‐dihydrodiol and B(a)P‐phenol metabolites. 7‐Ethoxyresorufin was, however, a very poor substrate for cytochrome P‐450lm2. Cytochrome P‐450lm3had less activity towards the investigated substrates while cytochrome P‐450lm4preferentially formed 2‐ and 3‐hexanol, resorufin and B(a)P‐9,10‐dihydrodiol. Cytochrome P‐450lm4isolated after pretreatment with 3‐methylcholanthrene or pheno‐barbital showed roughly the same characteristics except in the formation of 1‐hexanol where cytochrome P‐450lm4isolated after phenobarbital treatment was the most effective. The formation of B(a)P‐4,5‐ and −9,10‐dihydrodiols was greatly increased by incorporation of epoxide hydrase. Our results indicate a certain specificity of the different forms of cytochrome P‐450 in the live

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01634.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Several aspects of carbohydrate metabolism following 24 hr and 48 hr treatment with 10 and 20 mg/l of trichlorfon, were studied in hepatopancreas, mantle, intestine and foot of the snail,Lymnaea acuminata.Following treatment with the pesticide, the rate of oxygen consumption and concentration of glycogen were reduced, while the levels of lactic acid and reducing sugars were enhanced. Withdrawal of pesticide for 7 days following trichlorfon treatment (10 mg/l for 48 hrs) could not reverse these changes.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01635.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of an increase of the potassium content of the food on the natriuretic and diuretic effects of lithium and amiloride was examined in Wistar rats pretreated with the respective drugs for a period of three weeks. Lithium (60 mmol/kg) or amiloride (200 mg/kg) was added to the food and the animals had access to water and a 0.46 M NaCl solution. An increase of the potassium content of the food resulted in a potassium dose‐dependent increase of the natriuretic effect in both lithium‐treated and amiloride‐treated rats. The effect was temporary in lithium‐treated rats but persistent in amiloride‐treated rats. Lithium treatment resulted in a 10‐fold increase of the water intake compared to control rats and amiloride‐treated rats. An increase of the potassium intake reduced the water intake in the lithium‐treated animals and modestly increased the water intake in amiloride‐treated rats. The results show that the exaggerated natriuretic effect produced by administration of potassium to rats treated with lithium is not a specific phenomenon. It is suggested that a lowered ability of the kidneys to secrete potassium may be responsible for the exaggerated natriuretic response to potassium in amiloride‐ and l

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01636.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The lung uptake and modulating effects of KWD 2131 [1(3,5‐dihydroxyphenyl)‐2‐(1,1‐dimethyl‐2‐hydroxyethyl) amino ethanol], a β‐adrenergic agonist, on pulmonary perfusion flow and histamine release from anaphylactic guinea‐pig lungs were studied using an isolated perfused lung model. The lung extraction ratio, as calculated from the concentration of drug in the inflowing and outflowing medium in single pass studies was<0.05 at steady state which was achieved within 3 min. after start of drug infusion. Statistically significant protection to antigen elicited reduction in perfusion flow and inhibition of histamine release were obtained at the inflowing concentration 1.5 × 10−6mol/l but not at 1.5 × 10−7mol/l. The observed inhibition of the anaphylactic decrease in the perfusion flow can partly be explained by the decre

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01637.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:This study aimed to elucidate the mechanism by which Li+inhibits adenylate cyclase (AC)in vitro.It was found that Li+inhibited the norepinephrine‐ (NE) and the fluoride‐ (F) stimulated AC activities of rat fat cell ghosts at Li+concentrations above 10 mM. The basal enzyme activity was unaffected even at 80 mM of Li+. Li+inhibited the NE‐induced AC activity in a mainly non‐competitive way, but the inhibitory effect decreased with increasing concentrations of NE. The inhibition by Li+of both NE‐ and F‐‐stimulated AC activities was antagonized by Mg2+. The Mg2+antagonism of the Li+‐induced inhibition of the NE‐stimulated AC activity was independent of the NE concentration. Furthermore, Ca2+, inhibiting AC activity by a Mg2+antagonism, abolished the inhibitory effect of Li+. It is suggested that Li+affects both the Ka of NE and the Vmax of AC through 1) an inhibitory action of LiATP3‐at the catalytic site of AC or 2) an inhibitory action of Li+at an allost

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01638.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Twentyfour hours after the intraperitoneal injection of a single dose of allylisopropylacetamide (AIA) in amounts of 100 mg/kg or more to 30‐day old male Wistar rats, the livers of most of the animals showed an irregular yellow colouration and a fragile consistency. No macroscopic changes were detected following AIA doses of 25 or 50 mg/kg. Bromsulphthalein retention was not significantly increased after the administration of 25 mg/kg AIA, but distinctly enhanced after 400 mg/kg. Succinate‐dehydrogenase‐activity in liver homogenate was not altered after 25 mg/kg, but significantly decreased after 400 mg/kg. Ethylmorphine‐N‐demethylation activity was enhanced after small doses without increase of cytochrome P‐450 (cyt. P‐450) concentration and decreased after higher doses, accompanied by a remarkable cyt. P‐450 loss. GPT activity in serum and liver was not altered after both 25 and 400 mg/kg AIA. GOT activity was slightly but significantly enhanced both in serum and liver after the high dose of 400 mg/kg. Thus in addition to the well‐known cyt. P‐450 destruction other signs of hepatotoxicity co

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01639.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The renal excretion of sulphachlorpyridazine (SCP) was measured in 34 unanaesthetized piglets 5–74 days of age. The renal handling of SCP was found to include: glomerular filtration, active tubular secretion and passive reabsorption. During the age period studied the clearance of ultrafiltrable SCP increased several times more than GFR (inulin clearance) indicating that the balance between filtration, secretion and reabsorption is changed during postnatal maturation. The age‐related change in clearance ratio possibly reflects both a greater increase in tubular secretory capacity than in glomerular filtration and a relative decrease in the passive reabsorpt

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01640.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effects of 4‐hydroxypyrazole (4‐HP), a principal metabolite of pyrazole, were studied in mice. The compound was toxic, much more so than pyrazole with an LD50 of 1.1 mmol/kg (92 mg/kg) and doses greater than 1.5 mmol/kg (126 mg/kg) were almost invariably fatal. Toxicity seemed to be centred on the liver with microscopic evidence of centrolobular necrosis apparent. Mouse liver catalase was almost totally inhibited 1 hour after administration of 1 mmol/kg of 4‐HP. Tryptophan pyrrolase was also inhibited. 4‐HP seemed to penetrate into the brain as judged by inhibition of brain catalase activity. A slight increase in brain serotonin concentration was found but 4‐HP hadno effect in the doses used(l.5 mmol/kgor4× 1.0 mmol/kg)on brain or heart noradrenaline. We conclude that the pyrazole‐induced decrease in brain noradrenaline is not mediated via 4‐HP. Furthermore, simultaneous treatment with methanol and pyrazole, which prevents the formation of 4‐HP, did not prevent the decrease in brain noradrenaline levels. Since methanol prevented the pyrazole‐induced decrease in brain catalase activity, we can also rule out the possibility that the decrease in brain noradrenaline is secondary to pyrazole‐induced inhibition of brain catalase. It is concluded that though 4‐HP is an active metabolite of pyrazole, causing, in particular, the hepatotoxicity of the parent molecule, it is not responsible for all the varied biologic

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01641.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The metabolism of femoxetine, a serotonin uptake inhibitor, has been investigated in rats, dogs, monkeys, and human subjects using two14C‐femoxetine compounds with labelling in different positions. The metabolic pathways were oxidation (and glucuronidation) and demethylation, both reactions most probably taking place in the liver. Nearly all femoxetine was metabolised, and the same metabolites were found in urine from all four species. Only a small percentage of the radioactivity excreted in the urine was not identified. Rat and dog excreted more N‐oxide than monkey and man, while most of the radioactivity (60–100%) in these two species was excreted as two hydroxy metabolites. The metabolic pattern in monkey and man was very similar. About 50% was excreted in these two species as one metabolite, formed by demethylation of a methoxy group. A demethylation of a N‐CH3group formed an active metabolite, norfemoxetine. The excretion of this metabolite in urine from man varied from 0 to 18% of the dose between individuals. Most of the radioactivity was excreted with the faeces in rat and dog, while monkey and man excreted most of the radioactivity in urine. This difference in excretion route might be explained by the difference in the metabolic pattern. No dose dependency was observed in any of the three animal species inves

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01642.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:A detailed knowledge of fluoride (F) pharmakokinetics is necessary if its pharmacologic and toxicologic effects are to be adequately understood. In the present study plasma F concentrations have been analysed using repeated blood samples taken from the ethmoidal sinus of rats given 25,50,100 and 150 p.p.m. F in drinking waterad libitumfor 79 days. A close relationship between the F‐concentration in the drinking water and plasma F concentrations was found. When the administration of F was stopped, a rapid decline in plasma F concentration was noted during 48 hrs in all groups. The plasma F concentrations in the 25 p.p.m. group returned to preexperimental levels but remained elevated in the other groups. The F concentrations of dentin and bone were determined and calculated on a dry fat free basis. The results show that there was a close relationship between plasma, bone and dentin concentration

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1981.tb01643.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY