ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb01930.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The vasodilation mechanism induced by ketamine was investigated in isolated smooth muscle strips of rabbit portal veins. Ketamine inhibited both the phasic and tonic components of K+‐induced contraction at concentrations greater than 500 μM and 100 μM, respectively. This effect was reversible and concentration‐dependent with concentrations up to 1 mM. These effects were similar to those producd by verapamil. In the presence of 60 mM K+, application of Ca2+(2.5 mM) in the perfusing solution caused tonic contraction of the smooth muscle, and ketamine at concentrations larger than 10 μM strongly inhibited this Ca2+‐induced contraction. Ketamine (100 μM) also inhibited the K+‐induced contractions significantly in the absence and presence of guanethidine, tetrodotoxin and propranolol. Ketamine produced similar concentration‐dependent relaxations in the tissues with and without endothelium. These results indicate that in rabbit portal vein, vasodilation produced by ketamine is not endothelium‐dependent but is likely to be due to blockade of the voltage‐gated influx of e

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00094.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of various inotropic interventions on post‐rest potentiation and its decay were investigated in isolated cardiac muscle. The inotropic interventions studied were: reduced extracellular Na+ and elevated extracellular Ca2+concentration; exposure to ouabain, monensin, isoprenaline, phenylephrine and cirazoline. Force of contraction (stimulation frequency 2 Hz) was measured isometrically in left atria and right ventricular strips of rat hearts. Maximum post‐rest potentiation was reached after 10 sec. of rest and amounted to 245±26% of pre‐rest control in ventricle and 192±15% in atria. Ca2+‐recirculation fraction was calculated from the decay of post‐rest potentiation after resumption of regular stimulation, it was 0.77±0.01 in 11 control ventricular strips. High concentrations of caffeine (3 mmol/1) completely abolished post‐rest potentiation in both tissues. The development of post‐rest potentiation was accelerated in the presence of most of the inotropic agents. However, with the exception of ouabain and only in atrial muscle, none of the inotropic interventions produced higher post‐rest contraction amplitudes than during controls. In rat heart muscle, the inotropic interventions studied are not any more effective in augmenting force of contraction than prolonged stimulation intervals. This suggests that (1) the distribution of Ca2+into the sarcoplasmic reticulum is at a maximum during post‐rest potentiation; (2) modifications of signal transduction pathways cannot further increase post‐rest potentiation; and therefore that (3) shifts in Ca2+distribution ac

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00095.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:Retinoic acid (RA) and its congeners mediate their biologic effects after binding to nuclear transcription factors called retinoic acid receptors. Biological effects and binding affinities to various receptors vary widely. Activation of transcription ability for selected retinoids was investigated using a standardized model system. CV‐1 cells were cotransfected with a retinoic acid responsive reporter plasmid and expression vectors for retinoic acid receptors (RARs, α, β or γ) and/or retinoic X receptor (RXRα), and were treated with a retinoid (all‐tran‐RA, 13‐cis‐RA, Ro 12‐4894, SRI 5898‐21, or Ro 13‐7410). Gene transcription for all retinoids tested was activated in a dose‐dependent manner. All‐trans‐RA was the most potent activator of RARα while SRI 5898‐21 was the least active. RARa and RARβ showed similar levels of activation with all the retinoids tested, Ro 12‐4894 and Ro 13‐7410 induced little transcription in the presence of RARγ. Cotransfection of RXRα with the RARs changed the ability of the retinoids to activate transcription. Transcriptional activation in cells cotransfected with RXR and RARβ or RARγ was lower than in cells cotransfected with RARβ alone or RARγ alone. Such models with specific responsive elements may be useful for evaluating the relative activity of various retinoidsin vitro, however, complex interactions are likely depending on the choice of the reporter construct and other tran

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00096.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of the benzodiazepine receptor agonist diazepam, the benzodiazepine receptor antagonist flumazenil and the benzodiazepine receptor inverse agonist ethyl‐8‐azido‐5, 6‐dihydro‐5‐methyl‐6‐oxo‐4H‐imidazo‐[1, 5‐a] [1‐4]benzo‐diazepine‐3‐carboxylate (RO 15‐4513) on the locomotor activity and the behaviour of animals in the plus‐maze test were studied in sleep‐deprived mice. The effects of convulsants acting at GABA‐benzodiazepine‐barbiturate receptor complex‐bicuculline, picrotoxin and pentylenetetrazole, were also studied. Sleep deprivation of mice for 24 hr using the platform technique caused behavioural excitation that was reflected by an increase in the locomotor activity. Administration of diazepam (0.5 and 2.0 mg/kg), flumazenil (5.0 and 10.0 mg/kg) and RO 15‐4513 (1.0, 2.0 and 3.0 mg/kg) either did not affect (in low doses) or inhibited (in high doses) locomotions of control animals. The inhibition of locomotor activity by these drugs was greater in sleep‐deprived animals. In the plus‐maze test, diazepam in a dose of 2.5 mg/kg had an anxiolytic effect in control mice that was reflected by an increase in the percentage of entries onto and the percentage of time spent on the open arms of the plus‐maze. In contrast, in sleep‐deprived animals, diazepam did not induce anxiolytic action at any dose tested. In the highest dose (2.5 mg/kg) diazepam produced a sedative effect that was reflected by a decrease in the total number of entries made onto the open and into the closed arms of the plus‐maze. The convulsive actions of bicuculline (2.0–4.0 mg/kg) and picrotoxin (2.5–4.0 mg/kg) were considerably more pronounced in sleep‐deprived mice as compared to control animals. The effect of pentylenetetrazole (60–100 mg/kg) was not changed in sleep‐deprived mice. These data suggest that sleep deprivation induced a sensitization of mice to the motor depressant effect of benzodiazepine receptor agonists, antagonists and inverse agonists and to the convulsive action of bicuculline and picrotoxin. At the same time sleep deprivation induces a hyposensitivity of mice to the anxiolytic effect of diazepam. It is proposed that the hyposensitivity to the anxiolytic effect of diazepam as well as the hypersensitivity to the convulsions induced by bicuculline and picrotoxin in sleep‐deprived mice might be due to the alterations in the function of G

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00097.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The binding of the antipsychotic agent3H‐remoxipride to membranes of rat liver and brain (whole brain and cerebellum) was studied with filtration technique. Saturable high affinity binding was obtained for all three types of tissue preparations. Heterogenous binding sites were found since various types of compounds inhibited the binding of3H‐remoxipride with shallow dose‐response curves. In the liver preparation it was possible to differentiate between two different binding sites. One site, called rem1, was defined with 100 nM alaproclate and bound σ2ligands with high affinity, e.g. haloperidol, GBR 12909, DTG and (+)‐3‐PPP. High correlation (r=0.93) was obtained between the inhibition of the binding of3H‐remoxipride to the rem1site and the inhibition of the binding of the σ ligand3H‐DTG reported previously (Ross 1991), indicating that the rem1site is identical to a σ2‐like binding site. The other3H‐remoxipride binding site in the rat liver, rem2, appears to be identical to the site binding alaproclate, proadifen and cocaine with high affinity. Cd2+and Zn2+were potent inhibitors of both binding sites, Cd2+particularly of rem2binding and Zn2+preferably of rem1binding. The apparent Bmax(pmol/g original tissue) and KD(nM) values for rem1binding were 441±43 and 80±14, and for rem2binding 727±116 and 95±6. The binding of3H‐remoxipride to the brain preparations was also inhibited with shallow dose‐response curves. The Bmaxvalues for the preparations of whole brain and cerebellum were 67±15 and 71±9 pmol/g original tissue, respectively and the KDvalues were 171±19 and 176±6 nM. The IC50of the compounds were highly correlated to the IC50values for the rem1binding in the liver (r=0.96) and to IC50values for the inhibition of3H‐DTG binding in rat brain reported previously (Ross 1991). Cd2+and Zn2+ions also inhibited the binding of3H‐remoxipride in the brain preparation but at higher concentrations compared with the liver preparations. The present results indicate that the main part of the binding in the brain preparation

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00098.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of repeated exposure to 20 p.p.m.4‐tert‐butyltoIuene (CAS No. [98‐51‐1]) 6 hr/day for 14 days on the function of the intact nervous system were examined by measurements of flash evoked potentials in Wistar rats. The exposure to4‐tert‐butyltoluene induced changes in the amplitudes of the flash evoked potentials. The changes were significantly different from controls on day 2, 19 and 26 after cessation of the exposure, but not on day 5 and 12. No significant difference in body weight gain between groups was found during the experiment. These results indicate that repeated exposure to 20 p.p.m.4‐tert‐butyltoluene causes persistent changes in the function of the central nervous system measured as changes in the flash evoked potential. A reevaluation of the present TLV‐value of 10 p.p.m. for4‐tert‐buty

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00099.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of exposure to 800 or 4000 p.p.m. ofn‐heptane, CAS No. [142‐82‐5]) 6 hr per day during a period of 28 days, on the function of the auditory system were examined by measurements of auditory brain stem response (ABR) in Long Evans rats. The ABR was measured simultaneously with both needle electrodes and implanted electrodes. The wave forms recorded with the two types of electrodes were similar, but the amplitudes were largest on the recordings with implanted electrodes. The overall ratio between the amplitudes obtained with implanted electrodes and with needle electrodes was 1.4 for peak la and 2.5 for peak IV of the ABR. The exposure to rc‐heptane (4000 p.p.m.) reduced the amplitudes of components la and IV of the ABR. The reduction was most consistent for component IV and most pronounced at higher frequencies and intensities. The reduction in ABR corresponds to an increase in the auditory threshold of approximately 10 dB at all frequencies. Neither the latencies nor the interpeak latencies of components la and IV were changed. No significant changes in ABR were observed in the group exposed to 800 p.p.m. The mechanism behind the ototoxicity of organic solvents is di

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00100.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The current study was to answer the question: Is enough mercury absorbed from dental amalgam fillings to produce renal damage? One hundred healthy adults (18–44 years old) filled out health questionnaires and voided urine samples. Urine mercury concentration and N‐acetyl‐β‐glucosaminidase (NAG) were measured. Subjects were grouped into those having amalgam fillings (N=66) and those without (N=34). Median (95% Confidence Interval) urine mercury was 1 (1–2) and 0 (0–0.6) ng/ml (P<0.01) and median urine NAG was 23 (18–27) and 16 (11–18) units (P<0.05) in the two groups respectively. People with mercury amalgam fillings excreted slightly more mercury than people without them, and have a very small increase in urinary NAG excretion that is probably of no clinical significance. This dose of mercury absorbed from amalgam appears to be too little to be a public health hazard

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00101.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Abstract:The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemilumi‐nescence and spectrophotometric assays. The luminol‐dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O2−and H2O2production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol‐dependent chemiluminescence, and concomitantly O2−and H2O2production of neutrophils stimulated with formyl‐methionyl‐leucyl‐phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc‐induced O2−production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1‐(5‐isoquinolinesulfonyl)‐2‐methylpiperazine dihydrochloride (H‐7), or a calmodulin antagonist, N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalenesulfonamide (W‐7). These results suggest that zinc can augment luminol‐dependent chemiluminescence by increasing O2−production through the classical signal transduc

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1995.tb00102.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY