Differentiation between two ligands for peripheral benzodiazepine binding sites, [3H]R05-4864 and [3H]PK 11195, by thermodynamic studies

Fur, G. Le; Vaucher, Nadine; Perrier, M.L.; Flamier, A.; Bénavidès, J.; Renault, C.; Dubroeucq, Marie-Christine; Guérémy, C.; Uzan, A.

doi:10.1016/0024-3205(83)90794-4

Cited by 248 publications

(69 citation statements)

References 11 publications

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“…The level of TSPO protein in wild-type, empty plasmid-transfected and exogenous TSPO- transfected Jurkat cells, and positive control MDA-MB-231 cells was measured by membrane receptor binding using the TSPO ligand [3H]PK11195 24 . No difference between total and non-specific binding of [3H]PK11195 was found in the wild-type Jurkat cells, confirming the barely detectable level of endogenous TSPO protein in these cells (Fig.…”

Section: Resultsmentioning

confidence: 53%

Functional gains in energy and cell metabolism after TSPO gene insertion

et al. 2017

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Recent loss-of-function studies in tissue-specific as well as global Tspo (Translocator Protein 18 kDa) knockout mice have not confirmed its long assumed indispensability for the translocation of cholesterol across the mitochondrial inter-membrane space, a rate-limiting step in steroid biosynthesis. Instead, recent studies in global Tspo knockout mice indicate that TSPO may play a more fundamental role in cellular bioenergetics, which may include the indirect down-stream regulation of transport or metabolic functions. To examine whether overexpression of the TSPO protein alters the cellular bioenergetic profile, Jurkat cells with low to absent endogenous expression were transfected with a TSPO construct to create a stable cell line with de novo expression of exogenous TSPO protein. Expression of TSPO was confirmed by RT-qPCR, radioligand binding with [3H]PK11195 and immunocytochemistry with a TSPO antibody. We demonstrate that TSPO gene insertion causes increased transcription of genes involved in the mitochondrial electron transport chain. Furthermore, TSPO insertion increased mitochondrial ATP production as well as cell excitability, reflected in a decrease in patch clamp recorded rectified K channel currents. These functional changes were accompanied by an increase in cell proliferation and motility, which were inhibited by PK11195, a selective ligand for TSPO. We suggest that TSPO may serve a range of functions that can be viewed as downstream regulatory effects of its primary, evolutionary conserved role in cell metabolism and energy production.

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Section: Resultsmentioning

confidence: 53%

Functional gains in energy and cell metabolism after TSPO gene insertion

et al. 2017

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“…The efficacy of calcium chan nel blockers on ischemia and reperfusion-induced ventricular dysrhythmias in differ ent experimental preparations remains a matter of debate. Diazepam has been shown to decrease action potential duration by modulating calcium channel fluxes [34], Fur thermore, peripheral benzodiazepine recep tor antagonists may inhibit the actions of calcium channel blockers [35]. The impor tance of alterations in myocardial electro lytes on the etiology of reperfusion-induced arrhythmias has recently been discussed by Tosaki et al [36].…”

Section: Discussionmentioning

confidence: 99%

Effect of Alprazolam on Ischemia and Reperfusion-Induced Ventricular Arrhythmias in the Isolated Perfused Rat Heart

Kingma¹,

Kingma²

1989

Pharmacology

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The effects of the triazolobenzodiazepine anxiolytic, alprazolam, on the incidence of ischemia- and reperfusion-induced ventricular arrhythmias was studied in the isolated buffer-perfused rat heart. Administration of alprazolam before and after myocardial ischemia resulted in a dosage-dependent reduction in the incidence and duration of reperfusion-induced ventricular fibrillation and was significant at a concentration of 1 × 10^–3 mol/l alprazolam. This cardioprotective effect was not extended to ischemia-induced ventricular dysrhythmias. In conclusion, our findings provide evidence that benzodiazepine drugs are able to provide a cardioprotective effect in the experimental setting of myocardial ischemia followed by coronary reperfusion.

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“…Despite these variable intrinsic effects, PK11195 blocks the convulsant effects of Ro05-4864 (File and Mabbutt 1983;Seale et al 1987) and at least some of the effects of this compound in the hole-board test (File and Pellow 1983). Such findings lend some credence to the view that Ro05-4864 is an agonist, and PKl1195 an antagonist, at nonneuronal sites (LeFur et al 1983c). Our results show that, although without effect on basal tail-flick responding or behaviour displayed by intruders during encounters, PKl1195 totally blocks the analgesic consequences of defeat at doses of >__ 5 mg/kg.…”

Section: Discussionmentioning

confidence: 80%

Blockade of non-opioid analgesia in intruder mice by selective neuronal and non-neuronal benzodiazepine recognition site ligands

Rodgers

Randall

1988

Psychopharmacology

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In male mice, the biologically significant experience of social defeat is associated with an acute non-opioid form of analgesia. Recent studies have shown that this reaction is sensitive to certain benzodiazepine receptor ligands but is unaffected by others. The present experiments were designed to assess the possibility that activity at "non-neuronal" benzodiazepine binding sites might account for this unusual pharmacological profile. Our results show that defeat analgesia was blocked by clonazepam (0.06-3 mg/kg), Ro05-4864 (2.5-20 mg/kg), Ro05-5115 (20 mg/kg), PK11195 (5-20 mg/kg) and PK14067 (10-20 mg/kg). Furthermore, when given in combination, subthreshold doses of PK11195 (2.5 mg/kg) and clonazepam (0.03 mg/kg) totally prevented defeat analgesia. All of these effects were observed in the absence of intrinsic activity on basal nociception. Together with earlier findings, current data imply that inhibition of defeat analgesia by ligands for neuronal and/or non-neuronal benzodiazepine recognition sites is most probably unrelated to their activity at these sites. Alternative explanations for the overall patterns of results are considered.

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Differentiation between two ligands for peripheral benzodiazepine binding sites, [3H]R05-4864 and [3H]PK 11195, by thermodynamic studies

Cited by 248 publications

References 11 publications

Functional gains in energy and cell metabolism after TSPO gene insertion

Functional gains in energy and cell metabolism after TSPO gene insertion

Effect of Alprazolam on Ischemia and Reperfusion-Induced Ventricular Arrhythmias in the Isolated Perfused Rat Heart

Blockade of non-opioid analgesia in intruder mice by selective neuronal and non-neuronal benzodiazepine recognition site ligands

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