Characterization of peripheral type benzodiazepine binding sites in human and rat platelets by using [3H]PK 11195. Studies in hypertensive patients

Bénavidès, J.; Quarteronet, Dominique; Plouin, Pierre‐François; Imbault, F.; Phan, T.; Uzan, A.; Renault, C.; Dubroeucq, Marie-Christine; Guérémy, C.; Fur, G. Le

doi:10.1016/0006-2952(84)90719-6

Cited by 49 publications

(13 citation statements)

References 11 publications

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“…In vitro competition experiments performed in our laboratory have shown that haloperidol (up to 10 gM) is an ineffective displacer of 3H-PK t 1195 from PBS, similar to results reported by Benavides et al (1984). Thus, the alteration of PBS in brain can be attributed to a modulatory effect of chronic haloperidol treatment.…”

Section: Discussionsupporting

confidence: 84%

Effect of chronic haloperidol treatment on peripheral benzodiazepine binding sites in cerebral cortex of rats

Gavish

Weizman

Becker

et al. 1988

J. Neural Transmission

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The effects of 21 days of haloperidol treatment on central benzodiazepine (BZ) receptors in the cerebral cortex of rats and on peripheral-type BZ binding sites (PBS) in the cerebral cortex and heart of rats were studied. Neuroleptic treatment did not affect the maximal binding capacity or the affinity of the central BZ receptor to 3H-flunitrazepam. Chronic haloperidol treatment resulted in a significant increase of 38% in PBS density in the cerebral cortex, with no alteration in PBS density in the heart. No alteration in PBS affinity for its ligand 3H-PK 11195 was observed, either in the cerebral cortex or in the heart. The modulatory effect of chronic haloperidol administration on PBS density in the brain may be related to some of the neurobehavioral or hormonal effects of the drug.

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Section: Discussionsupporting

confidence: 84%

Effect of chronic haloperidol treatment on peripheral benzodiazepine binding sites in cerebral cortex of rats

Gavish

Weizman

Becker

et al. 1988

J. Neural Transmission

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“…Since hematopoietic cells, such as monocytes [25], polymorphonuclear neutrophils [26], lymphocytes [27], platelets [11], [28] and erythrocytes [29], too, express TSPO, it is likely that some of the TSPO gene expression found in whole bone is due to contaminating bone marrow which is difficult to fully remove from a mouse femur of 1 mm diameter. Therefore, pure primary osteoclasts derived from mouse spleen cells with M-CSF/RANKL treatment and osteoblasts derived from newborn mouse calvaria were examined for the presence of TSPO gene products.…”

Section: Resultsmentioning

confidence: 99%

The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

et al. 2012

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The presence of the translocator protein (TSPO), previously named as the mitochondrial or peripheral benzodiazepine receptor, in bone cells was studied in vitro and in situ using RT-qPCR, and receptor autoradiography using the selective TSPO ligand PK11195. In vitro, the TSPO is highly expressed in osteoblastic and osteoclastic cells. In situ, constitutive expression of TSPO is found in bone marrow and trabecular bone, e.g., spongiosa. Mice with a reduction of bone turnover induced by a 4-day treatment of osteoprotegerin reduces [3H]PK11195 binding in the spongiosa (320±128 Bq.mg−1, 499±106 Bq.mg−1 in saline-treated controls). In contrast, mice with an increase in bone turnover caused by a 4-day low calcium diet increases [3H]PK11195 binding in the spongiosa (615±90 Bq.mg−1).Further, our study includes technical feasibility data on [18F]fluoride microPET imaging of rodent bone with altered turnover. Despite [18F]fluoride having high uptake, the in vivo signal differences were small. Using a phantom model, we describe the spillover effect and partial volume loss that affect the quantitative microPET imaging of the small bone structures in experimental mouse models.In summary, we demonstrate the expression of TSPO in small rodent bone tissues, including osteoblasts and osteoclasts. A trend increase in TSPO expression was observed in the spongiosa from low to high bone turnover conditions. However, despite the potential utility of TSPO expression as an in vivo biomarker of bone turnover in experimental rodent models, our small animal PET imaging data using [18F]fluoride show that even under the condition of a good biological signal-to-noise ratio and high tracer uptake, the currently achievable instrument sensitivity and spatial resolution is unlikely to be sufficient to detect subtle differences in small structures, such as mouse bone.

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“…1977], A physically and pharma cologically distinct subset of BZ binding sites has also been identified in the CNS [Anholt et al, 1984;Marangos et al, 1982: Schoemaker et al 1981 as well as in various peripheral tissues including kidney and heart [Taniguchi et al, 1982], lung [Das et al, 1987] and plate lets [Benavides et al, 1984], These latter sites, desig nated 'peripheral BZ binding sites' are differentiated from 'central type' sites by their high affinity for the BZ derivative R05 4864 [Gallager et al, 1981;Schoemaker et al, 1981] and the isoquinoline carboxamide deriva tive PK 11195 [Benavides et al, 1983], but very low affinity for clonazepam, a compound active at central type BZ sites , Although the exact physiological functions of the pe ripheral BZ receptors are as yet unclear, evidence does exist suggesting that these sites may play a role in endo crine function. Endocrine organs, including the adrenal cortex , pituitary gland Pazos et al, 1986], interstitial tissue of the testis , as well as human term pla centa, an active endocrine organ during pregnancy [Fares and Gavish.…”

Section: Introductionmentioning

confidence: 99%

“…Human blood platelets, which have a high density of peripheral BZ binding sites [Benavides et al, 1984] are a convenient, accessible tissue to study the role of these sites in various pathological conditions. Using [3H]PK 11195 as a selective ligand, previous studies have de scribed significant reductions in the density of platelet peripheral BZ binding sites in schizophrenia [Gavish et al, 1986a;Weizman et al, 1986] and anxiety disorder .…”

Section: Introductionmentioning

confidence: 99%

Effect of Increasing Estradiol Levels on Platelet Peripheral Benzodiazepine Binding Sites in Women Undergoing Human Menopausal Gonadotropin Treatment

Diorio

Welner²,

Tulandi³

et al. 1990

Neuropsychobiology

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The effect of increasing serum estradiol levels on platelet [³H]PK 11195 binding was investigated to determine the influence of gonadal steroids on platelet peripheral benzodiapezine binding sites. Serum estradiol and platelet [³H]PK 11195 binding were determined in 10 anovulatory, but otherwise healthy women before and after treatment with human menopausal gonadotropin. Despite a 30-fold increase in posttreatment estradiol, the kinetic parameters of platelet [³H]PK 11195 binding (K_d, B_max) remained essentially unchanged. These data indicate that peripheral benzodiazepine binding sites on platelets are not influenced by elevated concentrations of estradiol. Thus, it is suggested that variations in circulating levels of this female gonadal steroid are likely not responsible for the modifications in platelet peripheral benzodiazepine binding sites seen in association with various disease states.

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Characterization of peripheral type benzodiazepine binding sites in human and rat platelets by using [3H]PK 11195. Studies in hypertensive patients

Cited by 49 publications

References 11 publications

Effect of chronic haloperidol treatment on peripheral benzodiazepine binding sites in cerebral cortex of rats

Effect of chronic haloperidol treatment on peripheral benzodiazepine binding sites in cerebral cortex of rats

The 18 kDa Translocator Protein (Peripheral Benzodiazepine Receptor) Expression in the Bone of Normal, Osteoprotegerin or Low Calcium Diet Treated Mice

Effect of Increasing Estradiol Levels on Platelet Peripheral Benzodiazepine Binding Sites in Women Undergoing Human Menopausal Gonadotropin Treatment

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