摘要:

Glutathione (GSH) binding to rat liver cytosol at two different protein concentrations and a range of GSH concentrations was determined using rapid ultrafiltration. Two binding sites and nonspecific binding were determined by computer fit of the data. The high-affinity site had a similar affinity and capacity for GSH as that of the GSH S-transferases. Using the converged parameters and an estimation of cytosolic protein content of the intact liver, simulation of the GSH-free fraction and the contribution and degree of saturation of the high-affinity binding site were estimated over a broad range of GSH concentrations. The findings predict that 70–75% of cytosol GSH is free and that the high-affinity site is saturated with GSH in the physiologic rang

ISSN:0031-7012    

DOI:10.1159/000137945

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Diethylether has previously been shown to inhibit several pathways of drug metabolism, including conjugation of paracetamol in isolated rat hepatocytes. Since overall paracetamol conjugation consists of pathways of different subcellular localization (cytosolar sulphation and microsomal glucuronidation) the response of both pathways to diethylether was tested. The elimination of paracetamol (160 µmol/l, initial concentration) and the formation of paracetamol sulphate and glucuronide were measured (high-performance liquid chromatography) in suspensions of isolated rat hepatocytes from fasted and fed animals over 1 h in the absence and presence of diethylether (30 mmol/l). Approximately 90% of the paracetamol elimination was by sulphation and nearly 10% by glucuronidation both in the controls and in the presence of ether. The overall disposition of paracetamol and the formation of sulphate were both reduced by about 50% in the presence of ether compared to the controls while the formation of glucuronide was reduced by 70%. The results were not influenced by the nutritional state of the animals before sacrifice. It is concluded that the inhibitory effect of ether on total paracetamol metabolism was mainly caused by reduced sulphation. Since microsomal glucuronidation was also inhibited by ether, both cytosolar and microsomal enzyme systems were sensitive to diethylether

ISSN:0031-7012    

DOI:10.1159/000137946

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effects of α-adrenergic agonists on 45Ca efflux from slices of rat liver were studied and the results compared to earlier studies on the rabbit aorta. Norepinephrine and phenylephrine (PE) cause a stimulation of 45Ca efflux which was due to α1-receptor activation. The mitochondrial uncoupler dinitrophenol (DNP) also stimulated 45Ca efflux while caffeine had little or no effect. PE and DNP effects were due to the release of intracellular 45Ca stores, and both agents released a similar quantity of Ca2+. 45Ca/40Ca exchange in both PE- and DNP-released sources was similar (t½ ≅ 16 min). DNP and PE effects were not additive, and previous exposure to one agent reduces the response to the other. These results suggest that α1-agonists and DNP release a common source of intracellular Ca2+ in rat liver. Since in rabbit aorta α-agonists primarily release Ca2+ from a nonmitochondrial source, our results suggest α1-receptors act via the generation of a Ca2+-releasing substance which subsequently mobilizes Ca2+ from different organelles in different

ISSN:0031-7012    

DOI:10.1159/000137952

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effect of probenecid on the plasma protein binding of methotrexate (MTX) has been examined in vitro. At concentrations ≧5 × 10–4M, 30%) in the plasma binding of MTX. It is suggested that in vivo this would lead to a greater dispersion into the tissues and a larger volume of distribution, and may be partly responsible for the longer MTX elimination half-life observed with concurrent administration of proben

ISSN:0031-7012    

DOI:10.1159/000137947

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

In 6 patients with severe left-sided cardiac failure the absorption of drug from digoxin tablets was assessed by simultaneous administration of a commercially available tablet and of an intravenous tracer dose before and during therapy. Lag time, peak time, and dose-normalized increase in plasma concentration did not change in spite of clinical improvement. Two independent measures of the extent of availability, based on plasma and urine measurements, also remained unchanged and their average was similar to that reported for normals. There was, however, a great interindividual variability in absorption. We conclude that the absorption of digoxin tablets is unchanged in patients with left-sided cardiac failure.

ISSN:0031-7012    

DOI:10.1159/000137948

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Helical strips of rabbit coronary and femoral arteries were used to determine whether Na-K pump inhibition would diminish relaxation in response to sodium nitroprusside. Ouabain (10-5M) decreased relaxation by 10–7M sodium nitroprusside from 87.0 ± 5.4 to 65.2 ± 9.1 % in coronary, and from 62.0 ± 6.9 to 32.8 ± 3.3% in femoral artery strips. A low Na solution and a K-free solution also decreased relaxation by sodium nitroprusside. Relaxation in response to K+, an index of Na-K pump activity in arterial smooth muscle, was enhanced in the presence of sodium nitroprusside. These results may reflect an interaction between sodium nitroprusside and the sarcolemmal Na-K pump of arterial smooth m

ISSN:0031-7012    

DOI:10.1159/000137949

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The distribution of 3H-spiroperidol binding sites within rabbit superior mesenteric artery was studied in normal as well as 6-hydroxydopamine (6-OHDA) sympathectomized animals using a histoautoradiographic technique. The labelled drug was located in the three layers of the artery (adventitia, media and intima), with the greater density in the media. In the adventitia the radiolabelled drug was located at the level of fibrous and connective cells. In the media 3H-spiroperidol was bound by smooth muscle cells and is found in the cellular membrane of the same cells. 6-OHDA administration causes an increase in the number of 3H-spiroperidol binding sites in the adventitia and as well as a 20–25% increase in the media. The possible existence of a direct dopaminergic innervation of the superior mesenteric artery is discusse

ISSN:0031-7012    

DOI:10.1159/000137950

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

In an attempt to elucidate the mechanism of wet dog shakes (WDS) produced by carbachol administered into the rat lateral brain ventricle, the effects of blockade of muscarinic and nicotinic receptors on shaking response and the effects of carbachol on central catecholaminergic, serotonergic (5-HT) and GABAergic functions were studied in rats. The muscarinic receptor antagonists, atropine and scopolamine attenuated WDS produced by carbachol, whilst a peripherally active muscarinic receptor antagonist, scopolamine methyl nitrate, failed to influence WDS. The nicotine antagonist, mecamylamine, did not affect WDS caused by carbachol either.

ISSN:0031-7012    

DOI:10.1159/000137951

出版商:S. Karger AG    

年代:1984

数据来源: Karger