ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01148.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01149.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effect of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) on D1and D2dopamine receptors was assayed usingin vitroquantitative autoradiography. D1receptor subtype was labeled using 1 nM of3H‐SCH 23390 and D2receptor subtype was labeled using 0.4 nM of3H‐spiroperidol. The results are compared to the effect of MPTP on the striatal levels of dopamine and its metabolites, in BL C57 mice. While 2 and 5 doses of MPTP 30 mg/kg/day intraperitoneally reduced the content of striatal dopamine and its metabolites, no modifications were detected in D2receptor subtype in any cerebral area studied. However, D1receptors were reduced in the substantia nigra 24 hr after the last of 2 doses, but not later. We suggest a compensatory mechanism of the surviving dopaminergic neurones as well as the participation of spare receptors. This would explain the lack of receptor modification after the lesion obtained as seen by the striatal reduction of dopamine and metabolites content, after MPTP a

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01150.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Pretreatment of cultured rat hepatocytes with dexamethasone markedly enhanced the acute cAMP response to glucagon, isoproterenol or forskolin. The effect of dexamethasone was apparent within 3‐6 hr and was maximal after 20‐30 hr. The amplification of the cAMP response to glucagon could also be produced by other glucocorticoids, with relative potency dexamethasone>>methylprednisolone>hydrocortisone. The increased cAMP response was associated with a reduced cAMP phosphodiesterase activity in cell lysates and a reduced effect of the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine in intact cells, indicating that the glucocorticoid pretreatment reduced cAMP degradation. However, the increase in response to glucagon in glucocorticoid‐treated cells was relatively larger than the increase in forskolin response and also larger than the decrease in phosphodiesterase activity, suggesting that other factors in addition to down‐regulation of phosphodiesterases was responsible for the effect. Cycloheximide abolished the difference in phosphodiesterase activity and cAMP response between dexamethasone‐treated and control cells. The results suggest that the glucocorticoids increase the ability of hepatocytes to accumulate cAMP due to protein synthesis‐dependent processes which at least in part involve reduced de

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01151.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:TOCP (triorthocresyl phosphate) inhibits carboxylesterase (CarbE) activity in rat plasma and liver and significantly increases soman, sarin and tabun toxicity. Application of these agents after TOCP caused strong additional inhibition of CarbE and cholinesterases (ChE) in rat red blood cells, plasma, liver, brain, diaphragm and intercostal muscle. After phenobarbital pretreatment, which induced CarbE activity in plasma and liver by 80% and that of plasma ChE by 33%, acute toxicity of soman and tabun was greatly decreased, while that of sarin remained unaffected.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01152.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Effects of alaproclate, an antidepressive substance and 5‐HT uptake blocker, was studied using intracellular and extracellular recording techniques. Possible effects on the excitability of CA1 pyramidal cells in slices from rat hippocampus were explored. Alaproclate increased the probability of firing to an orthodromic input, increased the membrane resistance and prolonged the action potential. Increased excitability was also observed in extracellular recording experiments. It is suggested that these effects are due to depression of potassium channels in the membran

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01153.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:Capsaicin injected intrathecally releases substance P from primary sensory nerve endings, and induces a pain related behaviour in mice consisting of licking, biting and scratching directed to the distal part of the body. This behavioural response was reduced by approximately 35% after intraperitoneal administration of clomipramine, 10 mg/kg, 1 hr in advance, and by 38% after repeated administration (10 mg/kg/day for 9 days). Twenty‐four hr after the last repeated clomipramine injection, the response after capsaicin was still reduced by 36%, indicating a long‐lasting effect of repeated treatment. The results indicate that clomipramine has analgesic properties against pain of central origin both after single‐dose and repeated administr

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01154.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The influence of the extracellular Mg on the slow regenerative potential induced by Ca removal was investigated by using rabbit SA node tissue treated with ouabain. When the SA node tissue was superfused with ouabain (10−5M), the preparation became quiescent. Further superfusion with Mg‐free and Ca‐free solution produced a small regenerative potential reaching 21±3 mV (n = 5). Superfusion with high Mg, Ca‐free solution containing 5.19 mM Mg inhibited the regenerative potential. Superfusion of the ouabain‐treated SA node tissue with Ca‐free (2 mM EGTA) solution containing normal Mg or Mg‐free, Ca‐free (2 mM EGTA) solution produced a slow regenerative potential reaching 45±2 mV (n = 5) or 44±3 mV (n = 5). Increasing the external Mg to 3.6 mM or 6.18 mM in the Ca‐free, EGTA solution caused a significant inhibition of slow regenerative potential. The addition of diltiazem (0.08 mM) blocked both normal action potential and slow regenerative potential induced by superfusion with Mg‐free, Ca‐free (2 mM EGTA) solution. These results suggest that Mg inhibits the development of the slow regenerative potential resulting from inward current

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01155.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The isolated perfused rat liver model was successfully used to study the clinical interaction observed between cyclosporin A (CsA) and erythromycin (ER). Three experimental studies were performed. In a “Control group”, isolated rat livers were perfused with 60 μg3H‐CsA for 20 min. In an “ER group”, isolated rat livers were simultaneously perfused with 60 μg3H‐CsA and 6.0 mg ER. In an “ER ind group”, rats were treated with ER for 5 days, conditions under which the P450IIIA gene subfamily, principally involved in CsA metabolism, was specifically induced, and isolated rat livers were perfused with 60 μg3H‐CsA for 20 min. Biological parameters of the liver model such as biliary flow, oxygen consumption and pH were similar whatever group of animals. Biliary excretion of total radiolabel (sum of CsA and all the metabolites = CsAT) was similar in both the “Control” and “ER” groups but significantly higher in the “ER ind” group with respectively 8.05±0.81%, 8.45±1.93% and 14.54±2.12% of the entire amount of infused drug excreted during 2 hr. Using a high performance liquid chromatography method which specifically resolves unchanged CsA from its metabolites, we demonstrated that, although similar amounts of radiolabelled material were excreted in both the “Control” and “ER” groups, the CsA/metabolite ratio was lower than 1.0 in the “Control group” and higher than 1.0 in the “ER group”, suggesting an inhibition of CsA metabolism by ER in the “ER group”. These data could explain the increase in CsA blood levels observed in the clinic following administration of high ER doses and

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01156.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY

摘要:

Abstract:The effects of long‐term administration of sub‐convulsive doses of aldrin, an organochlorinated pesticide, on seizure susceptibility of rats were studied. Results show that treatment with the pesticide made the rats more susceptible to sound‐induced seizures; an increment in post‐seizure depression time after maximal electroschock administration was also observed in aldrin‐treated animals. Aldrin administration displaced the control dose‐response curves constructed for amphetamine and pentylenetetrazol to the left and right, respectively; no differences were detected between control and aldrin‐treated rats for strychnine, picrotoxin or 3‐mercaptopropionic acid. The results, discussed in the light of the effects of aldrin on biogenic amines or on the electrophysiology of neurones suggested an involvement of both noradrenergic and alteration excitability of the CNS with the observed increments on seizure

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1989.tb01157.x

出版商:Blackwell Publishing Ltd    

年代:1989

数据来源: WILEY