Peripheral benzodiazepine receptors in suicide attempters

The ability to visualize the immune response with radioligands targeted to immune cells will enhance our understanding of cellular responses in inflammatory diseases. Peripheral benzodiazepine receptors (PBR) are present in monocytes and neutrophils as well as in lung tissue. We used lipopolysaccharide (LPS) as a model of inflammation to assess whether the PBR could be used as a noninvasive marker of inflammation in the lungs. Planar imaging of mice administrated 10 or 30 mg/kg LPS showed increased [123I]-( R)-PK11195 radioactivity in the thorax 2 days after LPS treatment relative to control. Following imaging, lungs from control and LPS-treated mice were harvested for ex vivo gamma counting and showed significantly increased radioactivity above control levels. The specificity of the PBR response was determined using a blocking dose of nonradioactive PK11195 given 30 min prior to radiotracer injection. Static planar images of the thorax of nonradioactive PK11195 pretreated animals showed a significantly lower level of radiotracer accumulation in control and in LPS-treated animals ( p < .05). These data show that LPS induces specific increases in PBR ligand binding in the lungs. We also used in vivo small-animal PET studies to demonstrate increased [11C]-( R)-PK11195 accumulation in the lungs of LPS-treated mice. This study suggests that measuring PBR expression using in vivo imaging techniques may be a useful biomarker to image lung inflammation.

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2-Phenyl-imidazo[1,2-a]pyridine derivatives as ligands for peripheral benzodiazepine receptors: stimulation of neurosteroid synthesis and anticonflict action in rats

British Journal of Pharmacology ◽

10.1038/sj.bjp.0702530 ◽

1999 ◽

Vol 127 (1) ◽

pp. 177-187 ◽

Cited By ~ 71

Author(s):

Mariangela Serra ◽

Paola Madau ◽

Maria Francesca Chessa ◽

Monica Caddeo ◽

Enrico Sanna ◽

...

Keyword(s):

Benzodiazepine Receptors ◽

Pyridine Derivatives ◽

Peripheral Benzodiazepine Receptors ◽

Stimulation Of

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Peripheral benzodiazepine receptors

Biomarkers of Environmentally Associated Disease ◽

10.1201/9781420032208.ch28 ◽

2002 ◽

Author(s):

Tom√°s Guilarte

Keyword(s):

Benzodiazepine Receptors ◽

Peripheral Benzodiazepine Receptors

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4′-Chlorodiazepam — Agonist of peripheral benzodiazepine receptors as a protecting factor in IL-1 induced deregulation of collagen biosynthesis in cultured human chondrocytes

European Journal of Pharmacology ◽

10.1016/j.ejphar.2010.08.018 ◽

2010 ◽

Vol 647 (1-3) ◽

pp. 31-36

Author(s):

Wojciech Miltyk ◽

Arkadiusz Surazynski ◽

Joanna Dondziło ◽

Jerzy Palka

Keyword(s):

Benzodiazepine Receptors ◽

Human Chondrocytes ◽

Collagen Biosynthesis ◽

Peripheral Benzodiazepine Receptors

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Characterization of the effects of AHN 086, an irreversible ligand of "peripheral" benzodiazepine receptors, on contraction in guinea-pig atria and ileal longitudinal smooth muscle

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-022 ◽

1989 ◽

Vol 67 (2) ◽

pp. 126-134 ◽

Cited By ~ 13

Author(s):

G. T. Bolger ◽

A. H. Newman ◽

K. C. Rice ◽

H. W. M. Lueddens ◽

A. S. Basile ◽

...

Keyword(s):

Smooth Muscle ◽

Guinea Pig ◽

Calcium Channels ◽

Benzodiazepine Receptors ◽

Significant Inhibition ◽

Bay K 8644 ◽

Longitudinal Smooth Muscle ◽

Peripheral Benzodiazepine Receptors ◽

Inotropic Responses ◽

Guinea Pig Atria

The effects of AHN 086 and its reversibly acting structural analogue Ro 5-4864 were studied in the spontaneously beating guinea-pig atria and field-stimulated guinea-pig ileal longitudinal smooth muscle in the presence and absence of dihydropyridine calcium channel modulators. The treatment of guinea-pig atria with AHN 086 followed by extensive washing did not alter contraction. However, AHN 086 (0.5 μM) potentiated (88%) the positive inotropic responses by BAY K 8644, an effect that was not reversed by extensive washing of the tissue. Higher concentrations of AHN 086 (> 2 μM) irreversibly inhibited the intropic, but not the chronotropic responses to BAY K 8644, nifedipine, and isoproterenol. Ro 5-4864 (10 μM) produced a reversible enhancement of the inotropic responses and block of the chronotropic responses to BAY K 8644. In guinea-pig ileal longitudinal smooth muscle, both AHN 086 and Ro 5-4864 reversibly inhibited field-stimulated contractions. Neither Ro 5-4864 nor AHN 086 affected the ability of nifedipine to inhibit field-stimulated contractions of ileal longitudinal smooth muscle. Treatment of intact atria with 5 μM AHN 086 followed by extensive washing resulted in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to peripheral benzodiazepine receptors and of [3H]nitrendipine binding to voltage-operated calcium channels, but did not affect [3H]dihydroalprenolol binding to β-adrenergic receptors on atrial membranes. The same treatment applied to intact ileal longitudinal smooth muscle affected neither [3H] (−)-quinuclidinyl benzilate binding to muscarine receptors nor [3H]nitrendipine binding, but did result in a significant inhibition (30–50%) of [3H]Ro 5-4864 binding to ileal longitudinal smooth muscle membranes. The pharmacology of AHN 086 suggests that there is a different relationship between peripheral benzodiazepine receptors and voltage-operated calcium channels in guinea-pig atria and ileal longitudinal smooth muscle.Key words: calcium channels, peripheral benzodiazepine receptors, dihydropyridines, benzodiazepines, dihydropyridine binding sites.

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