Characterization of specific binding sites for [<sup>3</sup>H]‐1,3‐di‐o‐tolyl‐guanidine (DTG) in the rat glioma cell line C6‐BU‐1

Georg, Andrea; Friedl, Arno

doi:10.1002/glia.440060403

Cited by 8 publications

(2 citation statements)

References 19 publications

(25 reference statements)

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“…ó Receptors are highly expressed in tumor cells, including breast, colon, lung, neural, prostrate and skin tumor cell lines (2,6,35,40,41,(57)(58)(59)(60)(61)76,123,131,144,153,158). In ad-dition, these receptors are particularly enriched in tumor cells that are proliferating (1,78,156,159).…”

Section: Antineoplastic Effectsmentioning

confidence: 99%

Review of the Pharmacological and Clinical Profile of Rimcazole

2004

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Rimcazole is a carbazole derivative that acts in part as a sigma receptor antagonist. Wellcome Research Laboratories introduced this compound during the 1980s when it was hypothesized to be a novel antipsychotic with an improved side effect profile. However, subsequent clinical trials demonstrated that rimcazole lacked efficacy in schizophrenic patients and it is now primarily used as an experimental tool. In addition to its actions as a sigma receptor antagonist, rimcazole also has high affinity for dopamine transporters, and in recent years it has served as a lead compound for the development of novel dopamine transporter ligands. Although rimcazole cannot be considered a selective ligand for sigma receptors, the recent development of other selective agonists and antagonists for sigma receptors have aided in clarifying the involvement of these receptors in the actions of rimcazole. Many of the physiological and behavioral effects of rimcazole can in fact be ascribed to its action as a sigma receptor antagonist, although there are exceptions. Rimcazole is likely to have a continued role in elucidating sigma receptor function in either in vitro or in vivo systems where sigma receptor-mediated effects can be studied independently of the influence of dopamine and serotonin transporters.

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Section: Antineoplastic Effectsmentioning

confidence: 99%

Review of the Pharmacological and Clinical Profile of Rimcazole

2004

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“…Sigma sites are non-opiate binding sites with high affinity for the selective ligand 1,3-ortho-di-tolylguanidine (DTG). The sites have been studied in guinea pig and rat (Connick et al, 1992) and in cell lines (Georg et al, 1992;Hellewell and Bowen, 1990;Vilner and Bowen, 1992;Wu et al, 1991). At least two subtypes, sigma sites 1 and 2, have been characterized, based on the affinity for specific sigma site ligands (Connick et al, 1992;Hellewell et al, 1990;Quirion et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective sigma ligands interfere with the glutamate‐activated NOS pathway in hippocampal cell culture

Lesage

Loore

Peeters

et al. 1995

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We studied neuroprotective properties of 12 structurally different sigma site ligands in primary rat hippocampal cell cultures and analyzed whether they interfere with glutamate-induced activation of the nitric oxide synthase (NOS) pathway. Neurotoxicity was triggered with 1 mM glutamate on day 8 of culture. Cells were treated with various concentrations of the compounds for 7 days before glutamate exposure (prolonged pretreatment), or during glutamate exposure (acute treatment). Protection was seen after prolonged pretreatment (long-term protection) with sabeluzole, opipramole, haloperidol, ifenprodil, fenpropimorph, carbetapentane, and tiospirone, with pIC50s of 7.30, 7.15, 6.87, 6.68, 6.66, 6.39, and 6.34, respectively. There was no protection with PD 128298, 1,3-ortho-di-tolylguanidine, BMY-14802, (+)3-(3-hydroxyphenyl)-N-1(propyl) piperidine, or dextromethorphan. Upon acute treatment, only ifenprodil was protective. Interference of the drugs with glutamate activation of the NOS pathway was determined by measuring glutamate-activated cGMP formation and citrulline levels. Glutamate-activated cGMP formation was reduced by all neuroprotective sigma ligands after prolonged pretreatment but not after acute treatment. Sigma ligands added to cell culture lysate did not reduce citrulline formation, evidence that there was no direct effect on the NOS enzyme. We conclude that some but not all sigma ligands exert long-term protective properties against glutamate-induced neurotoxicity in primary hippocampal cultures, and that this protection is accompanied by attenuation of cGMP formation in the NOS pathway. However, inhibition of cGMP formation by itself appeared not sufficient for obtaining neuroprotective effects, as inhibition of glutamate-activated cGMP formation by N omega-nitro-L-arginine, haemoglobin, or PD128298 did not provide neuroprotection.

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Sigma1 binding in a human neuroblastoma cell line

et al. 1996

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Behaviorally, sigma1 agents modulate opioid analgesia. To examine possible mechanisms responsible for these interactions, we have identified a cell line containing both sigma1 and opioid receptors. [3H](+)-pentazocine binding in BE(2)-C human neuroblastoma cells is high affinity (KD 3.4 +/- 0.7 nM) and high density (Bmax 2.98 +/- 0.14 pmol/mg protein). Competition studies reveal a selectivity profile similar to that of sigma1 sites in guinea pig brain. (+)-Pentazocine has no effect upon either basal or forskolin-stimulated cyclase in the BE(2)-C cells, but cAMP accumulation is inhibited by the morphine, DPDPE and naloxone benzoylhydrazone. (+)-Pentazocine at concentrations as high as 10 microM does not affect this opioid effect, implying that sigma1/opioid interactions are not mediated at the level of the cell. This suggest that their behavioral interactions result from interacting neural circuits. Although (+)-pentazocine is without effect in the cyclase system, it does block carbachol-stimulated phosphoinositol turnover (IC50 6.5 +/- 1.14 microM). The specificity of the effect is confirmed by the ability of haloperidol (1 microM) to shift the IC50 value of (+)-pentazocine 2-fold to the right.

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Characterization of specific binding sites for [³H]‐1,3‐di‐o‐tolyl‐guanidine (DTG) in the rat glioma cell line C6‐BU‐1

Cited by 8 publications

References 19 publications

Review of the Pharmacological and Clinical Profile of Rimcazole

Review of the Pharmacological and Clinical Profile of Rimcazole

Neuroprotective sigma ligands interfere with the glutamate‐activated NOS pathway in hippocampal cell culture

Sigma1 binding in a human neuroblastoma cell line

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Characterization of specific binding sites for [3H]‐1,3‐di‐o‐tolyl‐guanidine (DTG) in the rat glioma cell line C6‐BU‐1

Cited by 8 publications

References 19 publications

Review of the Pharmacological and Clinical Profile of Rimcazole

Review of the Pharmacological and Clinical Profile of Rimcazole

Neuroprotective sigma ligands interfere with the glutamate‐activated NOS pathway in hippocampal cell culture

Sigma1 binding in a human neuroblastoma cell line

Contact Info

Product

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Characterization of specific binding sites for [³H]‐1,3‐di‐o‐tolyl‐guanidine (DTG) in the rat glioma cell line C6‐BU‐1