ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00741.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The kinetic deuterium isotope effect, D(V/K), on ethanol oxidation was measured on hepatocytes from rat and pig by the radiometric competitive method using14C‐labelled ethanol containing deuterium in the (1‐R)‐position. The corrected D(V/K) values of 2.68 and 2.80 for rat and pig hepatocytes respectively were significantly different, suggesting differences in the amount of non‐ADH ethanol oxidizing activity. The apparent isotope effects declined rapidly with time when acetaldehyde was present in the medium as a result of the reduction to ethanol of the [14C]‐acetaldehyde formed from the double labelled ethanol by alcohol dehydrogenase (ADH). Fructose and cyanamide caused the acetaldehyde concentration during ethanol oxidation to increase by entirely different mechanisms, and the isotope effect to decrease with time, as did also the addition of acetaldehyde. The apparent first order rate constant for the reverse ADH reaction, assuming the reactants to be acetaldehyde and the ADH‐NADH complex, was determined by two methods giving comparable results. In the presence of semicarbazide, which removes acetaldehyde, the isotope effect was nearly constant. This was the case also when the acetaldehyde concentration was very low (<1 μM) for other reasons, as in hepatocytes from starved animals. A mathematical formula describing the expected decrease of the apparent isotope effect with time was derived. The different response of pig and rat hepatocytes to addition of fructose (the ‘fructose effect’) is suggested to be caused by differences in activity of aldehyde dehydrogenases in

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00742.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The nigrostriatal toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) causes selective destruction of pigmented monoaminergic neurons of the brain, mainly in the substantia nigra. Primates and amphibians, whose nerve cells contain melanin, have shown a higher sensitivity for the toxic effects of MPTP than species which are lacking neuromelanin, e.g. rodents. In the present study the distribution after intraperitoneal injection of3H‐MPTP in frogs (Rana temporaria) was studied by whole‐body autoradiography. Histochemical staining methods for melanin were used in order to identify the pigment in various tissues. Melanin‐containing nerve cells were present bilaterally in the ventral motor parts of the frog brain. Melanin was also found in the meninges, around the cerebral ventricles and the aqueducts, and in the eyes, skin and liver. The results from the autoradiographic study of3H‐MPTP revealed a high accumulation and retention in all melanin‐containing structures up to 15 days after administration (the longest survival time). The pigmented tissues showed the highest concentration of radioactivity in the body at all survival times. The MPTP‐induced destruction of pigmented nerve cells may be related to the binding and storage of MPTP and/or its metabolites in neuromelanin, causing toxic cytoplasmic concentrations through the continuous release of substance f

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00743.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Glutathione (GSH) inhibited lipid peroxidation induced by NADPH‐BrCCl3in vitamin E sufficient microsomes, but did not in phenobarbital (PB)‐treated microsomes (containing about 60% of normal vitamin E) or in vitamin E‐deficient microsomes (containing about 30% of normal vitamin E). There was a good correlation between the increased formation of CHCl3from BrCCl3in the presence of GSH under anaerobic conditions and the vitamin E level in the microsomes. A normal level of vitamin E in microsomes was thus very important for GSH‐dependent inhibition of lipid peroxidation and for the efficient formation of CHCl3from BrCCl3. Bromosulfophthalein (BSP) eliminated the effects of GSH on lipid peroxidation and CHCl3formation. The apparent Km and Vmax of substrates for GSH S‐transferase were changed byin vivodepletion of vitamin E in microsomes, and the Vmax/Km values were significantly reduced. The enzyme activity in microsomes was inactivated following the loss of vitamin E duringin vitrolipid peroxidation, and GSH prevented the loss of vitamin E and protected the enzyme from attack by free radicals. GSH inhibited lipid peroxidation induced by NADPH‐Fe2+and the loss of GSH S‐transferase activity during the peroxidation in PB‐treated microsomes, but did not in the case of induction by NADPH‐BrCCl3. A possible relation between the microsomal GSH S‐transferase activity and defense by GSH against lipid peroxidation in micr

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00744.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The purpose of this study was to examine the effects of various adrenergic agonists and antagonists upon rat parotid oxygen consumption. The experiments were performed using collagenase‐isolated acini, and the O2consumption was determined using a Gilson Oxygraph 5/6 H with a Clark electrode. Stimulation with the α‐ and β‐adrenergic agonist adrenaline (10 μM) lead to a 65% increase in parotid O2consumption in about 10 sec. Addition of adrenaline after preincubation with the β‐adrenergic antagonist propranolol or the α‐adrenergic antagonist prazosin showed that about 2/3 of the adrenaline‐induced O2consumption originated in α‐adrenergic activity, whereas the remaining 1/3 stemmed from β‐adrenergic activity. Correspondingly, it was found that stimulation by the β‐adrenergic agonist isoprenaline (10 μM) increased the O2consumption with approximately 22%. Stimulation with the α‐adrenergic agonist phenylephrine (10 μM) did however, only increase O2consumption with 21%. This finding is probably not related to the existence of α‐2‐adrenoceptors stimulated by adrenaline and not by phenylephrine, since: (1) the adrenaline‐induced response was unaffected by preincubation by pertussis toxin, (an activator of the Giprotein of the adenylate cyclase complex), and (2) the stimulating effect of clonidine (an α‐2‐adrenoceptor agonist) was inhibited by preincubation with prazosin, and (3) radioligand binding studies using [3H]‐yohimbine was unsuccessful in demonstrating parotid α‐2‐adrenoceptors. Accordingly, a conclusion that accounts for the findings in this paper is that only β‐ and α1‐adrenoceptors are functioning in the parotid ac

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00745.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effects of 11 isomers of methylsulfonyl polychlorinated biphenyls (MSF‐PCBs) on the aryl hydrocarbon hydroxylase (AHH) activity were examined at a fixed dose of 1.5 μg/ml by using cultured lymphoblastoid cells. One of the isomers 3‐MSF‐3′,4,4′,5‐tetraCB, as well as 4‐MSF‐3,3′,4′,5‐tetraCB and 4‐MSF‐3,3′,4′,5,5′‐pentaCB, effectively reduced the AHH activity when added to the culture medium, especially that previously treated with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) to induce the AHH activity. However, the inhibitory potencies exerted by the above three MSF‐PCB compounds were smaller than that by 7,8‐benzoflavone (BNF). When added to the culture medium simultaneously with TCDD or 3‐methylcholanthrene (MC), 3‐MSF‐3′,4,4′,5‐tetraCB blocked the enhancement of the AHH activity by TCDD but did not that by MC. This is in contrast to BNF which blocked the increases due to both TCDD and MC. On the other hand, 3‐MSF‐3′,4,4′,5‐tetraCB added directly to the reaction mixture for the TCDD‐induced AHH activity showed little influence, while BNF decreased the same activity. These results imply that the effect of 3‐M

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00746.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

It was recently observed that the relaxation induced by glyceryl trinitrate (GTN) showed a biphasic concentration‐response curve; a high‐sensitivity component represented by concentrations1 nM. The effect of two glyceryl trinitrate concentrations (0.1 nM and 1 μM) were tested on the uptake of45Ca2+to tissue pieces of bovine mesenteric arteries (BMA) as well as on the uptake of45Ca2+to a microsomal preparation of BMA. The effect of GTN and 8‐Br‐cGMP was also studied on the IP3‐induced release of Ca2+from the microsomal preparation preloaded with45Ca2+. The influence of IP3and GTN on the activity of Ca2+‐ATPase in the microsomal preparation was tested as well. The phenylephrine‐stimulated uptake of Ca2+to tissue pieces of BMA was significantly reduced by the high GTN‐concentration (1 μM) but not by the lower concentration. The uptake of Ca2+to the microsomal preparation was significantly stimulated by the two GTN‐concentrations tested, as well as by 8‐Br‐cGMP (0.1 mM). The calcium release induced by IP3(1 μM) from the microsomal preparation was inhibited by both the low and the high GTN‐concentration and by 8‐Br‐cGMP (0.1 mM). The Ca2+‐ATPase activity was stimulated by both GTN‐concentrations tested while it was inhibited by IP3. It is concluded that GTN is able to induce a reduction of the free intracellular Ca2+by several mechanisms, which are of importance for the relaxation represented by the high‐affinity component. The low‐affinity component in addition reduces th

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00747.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The effects of seven‐day subcutaneous infusion of an α2‐adrenoceptor agonist, medetomidine, and an α2‐adrenoceptor antagonist, atipamezole, on the voluntary alcohol consumption of alcohol‐preferring rats were studied. The drugs were administered by means of implanted osmotic minipumps. Sham‐operated control rats had no pumps implanted. The rats had a free choice between 10% alcohol and plain water for 30 days before pump implantation and again for six days starting 24 hr after the operation. Atipamezole increased the alcohol consumption during the first day of free choice. Medetomidine had no significant effect. During the remaining period of infusion, the alcohol consumption did not differ from that preceding the pump implantation in each treatment group. Animals in the atipamezole group gained more weight during the seven‐day trial than did those in the medetomidine and control groups. The amine changes in different regions of the brain were consistent with medetomidine decreasing and atipamezole increasing the noradrenaline turnover. The present results indicate that specific drugs acting on the α2‐adrenoceptors produce only minor changes in the voluntary alcohol drinking of alcohol

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00748.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Species differences and mechanisms of 1,2‐dibromo‐3‐chloropropane (DBCP) nephrotoxicity were investigated by studying DBCP renal necrosis and DNA damage, distribution and glutathione‐dependent metabolism in rats, mice, hamsters and guinea pigs. Extensive renal tubular necrosis was observed in rats 48 hr after a single intraperitoneal administration (21–170 μmol/kg) of DBCP. Significantly less necrosis was found in mice and guinea pigs, whereas no renal damage was evident (21 μmol/kg DBCP), whereas in mice and hamsters a 10–50 times higher DBCP dose was needed to cause a similar degree of DNA damage. Renal DBCP concentrations at various time‐points (20 min., 1, 3 and 8 hr) after intraperitoneal administration (85 μmol/kg) revealed that the initial (20 min.) DBCP concentration was substantially higher in rats and guinea pigs compared to the other two species. Furthermore, kidney elimination of DBCP occurred at a significantly lower rate in rats than in mice, hamsters and guinea pigs. Cytosols from all four species debrominated DBCP at appreciable rates in the presence of glutathione (GSH), with kidney preparations from rats and guinea pigs being approximately two to three times more active than those from mice and hamsters. The present findings strengthen the hypothesis that DNA damage may be an initial event in DBCP organ toxicity. The extent and persistence of the DNA damage must, however, exceed a critical value to cause cell death. The high initial renal concentration of DBCP, its relatively long half‐life in the kidney and the ability of the kidney to activate DBCP in the presence of GSH all contribute to the high susceptibility of the rat kidney to DBCP

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00749.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The distribution of approximately equipotent doses of14C‐labelled clodronate (0.1 mmol/kg), etidronate (0.1 mmol/kg), and amidronate (0.015 mmol/kg), and also an equimolar dose of amidronate (0.1 mmol/kg), was studied in mice by measuring the14C‐activities in various tissues up to 360 days after a single intravenous injection. With the higher dose of amidronate the distribution could be, however, monitored only for 7 days because of the toxicity of the drug. The results indicate that there are major differences in the deposition of the bisphosphonates into soft tissues, while the disappearance from plasma and incorporation into bone are quite similar in terms of percentage of dose per g of tissue. However, the binding capacity of bone for clodronate and etidronate is many times greater than that for amidronate expressed as nmol of the drug per g of tissue. Amidronate deposits in the spleen and liver of mice, when injected in saline, whereas clodronate and etidronate do not. This agrees with the suggestion that amidronate, but not the other two, can interfere with the mononuclear phagocyte system of spleen and li

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00750.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY