Peripheral type benzodiazepine receptors and response to adenosine on the guinea-pig isolated trachea

Advenier, C.; Devillier, Philippe; Blanc, Marie; Gnassounou, J. P.

doi:10.1016/0952-0600(90)90044-j

Cited by 10 publications

(6 citation statements)

References 34 publications

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“…Frontal affinity chromatography - was carried out on MMAC-(U87MG) using multiple concentrations of DIPY, a TSPO specific high-affinity ligand [29-31]. The calculated binding affinity ( K d ) was 1.12 ± 0.15 μM (Table 1), which is consistent with the previously reported K i value of 0.68 μM (Table 2) [29].…”

Section: Resultssupporting

confidence: 79%

The development of mitochondrial membrane affinity chromatography columns for the study of mitochondrial transmembrane proteins

et al. 2015

Analytical Biochemistry

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Mitochondrial membrane fragments from U-87 MG (U87MG) and HEK-293 cells were successfully immobilized on to Immobilized Artificial Membrane (IAM) chromatographic support and surface of activated open tubular (OT) silica capillary resulting in mitochondrial membrane affinity chromatography (MMAC) columns. Translocator protein (TSPO), located in mitochondrial outer membrane as well as sulfonylurea and mitochondrial permeability transition pore (mPTP) receptors, localized to the inner membrane, were characterized. Frontal displacement experiments with multiple concentrations of dipyridamole (DIPY) and PK-11195 were run on MMAC-(U87MG) column and the binding affinities (Kd) determined were 1.08 ± 1.49 and 0.0086 ± 0.0006 μM respectively, which was consistent with previously reported values. Further, binding affinities (Ki) for DIPY binding site were determined for TSPO ligands, PK-11195, mesoporphyrin IX, protoporphyrin IX and rotenone. Additionally, the relative ranking of these TSPO ligands based on single displacement studies using DIPY as marker on MMAC-(U87MG) was consistent with the obtained Ki values. The immobilization of mitochondrial membrane fragments was also confirmed by confocal microscopy.

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Section: Resultssupporting

confidence: 79%

The development of mitochondrial membrane affinity chromatography columns for the study of mitochondrial transmembrane proteins

et al. 2015

Analytical Biochemistry

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“…The presence of TSPO in alveolar type II cells may be related to the increased secretion of surfactant through its effects on increased Ca 2+ efflux (Das and Mukherjee 1999). Moreover, TSPO drug ligands were shown to modulate the relaxation response of the guinea pig isolated trachea to adenosine (Advenier et al 1990). …”

Section: Resultsmentioning

confidence: 99%

Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription

2012

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Translocator protein (TSPO), previously known as the peripheral-type benzodiazepine receptor, is a ubiquitous drug- and cholesterol-binding protein primarily found in the outer mitochondrial membrane as part of a mitochondrial cholesterol transport complex. TSPO is present at higher levels in steroid-synthesizing and rapidly proliferating tissues, and its biological role has been mainly linked to mitochondrial function, steroidogenesis, and cell proliferation/apoptosis. Aberrant TSPO levels have been linked to multiple diseases, including cancer, endocrine disorders, brain injury, neurodegeneration, ischemia-reperfusion injury, and inflammatory diseases. Investigation of the functions of this protein in vitro and in vivo have been mainly carried out using high-affinity drug ligands, such as isoquinoline carboxamides and benzodiazepines, and more recently, gene silencing methods. To establish a model to study the regulation of Tspo transcription in vivo, we generated a transgenic mouse model expressing green fluorescent protein (GFP) from Aequorea coerulescens under control of the Tspo promoter region (Tspo-AcGFP). The expression profiles of Tspo-AcGFP, endogenous TSPO, and Tspo mRNA were found to be well correlated. Tspo-AcGFP synthesis in the transgenic mice was seen in almost every tissue examined, and as with TSPO in wild-type mice, Tspo-AcGFP was highly expressed in steroidogenic cells of the endocrine and reproductive systems, epithelial cells of the digestive system, skeletal muscle, and other organs. In summary, this transgenic Tspo-AcGFP mouse model recapitulates endogenous Tspo expression patterns and could be a useful, tractable tool for monitoring the transcriptional regulation and function of Tspo in live animal experiments.

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“…On the other hand. the same compound RP 52028 has been reported to inhibit the potentiation by diazepam of the relaxant effect of adenosine on the guinea-pig isolated trachea (Advenier et al, 1990). Therefore, the type of the benzodiazepine site involved in the potentiation of the a@-methylene ATP induced contraction of the guinea-pig isolated trachea as well as the mode of action of dipyridamole and the benzodiazepine compounds need further investigation to be fully characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Benzodiazepines have been shown to potentiate the relaxation induced by adenosine (10-5 to 10-3 M) on the guinea-pig isolated trachea. It was hypothesized that this effect involved a peripheral benzodiazepine receptor site because the rank order of potency of benzodiazepines was Ro5-4864 (an agonist of peripheral benzodiazepine receptors) > diazepam > clonazepam (an agonist of central benzodiazepine receptors) and because PK 11 195 (or RP S2028), an antagonist of peripheral benzodiazepine receptors, specifically inhibits these effects (Advenier et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Contractile effect of α,β‐methylene ATP on the guinea‐pig isolated trachea

Candenas¹,

Devillier²,

Naline³

et al. 1992

Fundamemntal Clinical Pharma

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The effects of alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-methylene ATP), 2-chloroadenosine and R-PIA (N6-(L-2-phenylisopropyl)-adenosine) and their interaction with dipyridamole, indomethacin, 8-phenyl-theophylline, diazepam and other agonists of central or peripheral benzodiazepine receptors were studied on the guinea-pig isolated trachea. alpha,beta-methylene ATP exerted contractile effects on the guinea-pig isolated trachea; - log EC50 and E(max) values were 8.86 +/- 0.19 and 31.3 +/- 2.3 (n = 31) (% vs acetylcholine 10(-3) M) respectively. In comparison with other purinergic receptor agonists, the rank order of potency was: alpha,beta-methylene ATP greater than 2-chloroadenosine greater than R-PIA. alpha,beta-methylene ATP and 2-chloroadenosine had significantly (P less than 0.05) greater efficacy (E(max)) than R-PIA. Indomethacin (3 x 10(-6) M) and 8-phenyltheophylline (10(-7) to 10(-5) M) significantly reduced the contractile effect of 2-chloroadenosine and R-PIA but did not affect alpha,beta-methylene ATP-induced contraction. Conversely, dipyridamole significantly reduced (10(-7) M) or suppressed (10(-6) M) the contractile effects of alpha,beta-methylene ATP whereas it only partially reduced (10(-6) M) the contractile effects of high concentrations of 2-chloroadenosine or R-PIA. Diazepam potentiated the efficacy of alpha,beta-methylene ATP. The E(max) (% vs acetylcholine 10(-3) M) values were 26.1 +/- 2.0 (n = 10) in control conditions and 45.9 +/- 4.6 (n = 5; P less than 0.05) in the presence of diazepam 10(-5) M. Diazepam did not modify the contractile effects of 2-chloroadenosine or R-PIA. Ro5-4864 (10(-7) to 10(-5) M), an agonist of peripheral benzodiazepine receptors, potentiated the contractile effects of alpha,beta-methylene ATP to the same extent as diazepam. Clonazepam, an agonist of central benzodiazepine receptors, did not modify these effects. Antagonists of central (flumazenil) or peripheral (RP 52028) benzodiazepine receptors had no influence on the interaction between diazepam or Ro-4864 and alpha,beta-methylene ATP. In conclusion, alpha,beta-methylene ATP exerts on guinea-pig isolated trachea a contractile effect which is not modified by indomethacin and 8-phenyltheophylline, but is reduced by dipyridamole. It is suggested that this effect might involve P2 chi receptor stimulation.

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Peripheral type benzodiazepine receptors and response to adenosine on the guinea-pig isolated trachea

Cited by 10 publications

References 34 publications

The development of mitochondrial membrane affinity chromatography columns for the study of mitochondrial transmembrane proteins

The development of mitochondrial membrane affinity chromatography columns for the study of mitochondrial transmembrane proteins

Translocator protein (Tspo) gene promoter-driven green fluorescent protein synthesis in transgenic mice: an in vivo model to study Tspo transcription

Contractile effect of α,β‐methylene ATP on the guinea‐pig isolated trachea

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