Lung Tissue Mitochondrial Benzodiazepine Receptors Increase in a Model of Pulmonary Inflammation

Audi, Said H.; Dawson, Christopher A.; Ahlf, Susan B.; Roerig, David L.

doi:10.1007/s004080000098

Cited by 8 publications

(5 citation statements)

References 27 publications

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“…The different mean transit times and variances were estimated as previously described (3,5). The Q D is a virtual volume that is equal to the product of a physical tissue volume and a tissueto-perfusate partition coefficient (1).…”

Section: Effects Of Hyperoxia On Dqh 2 Extravascular Volume Vascularmentioning

confidence: 99%

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs

Audi

Bongard²,

Krenz³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

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Section: Effects Of Hyperoxia On Dqh 2 Extravascular Volume Vascularmentioning

confidence: 99%

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs

Audi

Bongard²,

Krenz³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Carbon-11 labeled compound 1 was used for the in vivo imaging of microglial/macrophage activation present in different brain disorders including tumors by means of positron emission tomography (PET) – . In addition, a potential role for compound 1 and more in general for PBR in the in vivo monitoring of macrophage infiltration in respiratory disorders has been recently proposed – . These results have stimulated the research and development of a large number of potential PET radiotracers based on PBR ligands in different laboratories all over the world (for a recent review, see ref ).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Characterization of Novel 2-Quinolinecarboxamide Ligands of the Peripheral Benzodiazepine Receptors Bearing Technetium-99m or Rhenium

et al. 2008

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Potential receptor imaging agents based on Tc-99m for the in vivo visualization of the peripheral benzodiazepine receptor (PBR) have been designed on the basis of the information provided by the previously published structure-affinity relationship studies, which suggested the existence of tolerance to voluminous substituents in the receptor area interacting with 3-position of the quinoline nucleus of 2-quinolinecarboxamides 5. In the first step of the investigation, the stereoelectronic features of the above-indicated receptor area were also probed by means of 4-phenyl-3-[(1-piperazinyl)methyl]-2-quinolinecarboxamide derivatives bearing different substituents on the terminal piperazine nitrogen atom (compounds 6a-f). The structure-affinity relationship data confirmed the existence of a tolerance to bulky lipophilic substituents and stimulated the design of bifunctional ligands based on the 4-phenyl-3-[(1-piperazinyl)methyl]-2-quinolinecarboxamide moiety (compounds 6h,j,k,m). The submicromolar PBR affinity of rhenium complexes 6j,m suggests that the presence of their metal-ligand moieties with encaged rhenium is fairly compatible with the interaction with the PBR binding site. Thus, in order to obtain information on the in vivo behavior of these bifunctional ligands, (99m)Tc-labeled compounds 6h,k were synthesized and evaluated in preliminary biodistribution and single photon emission tomography (SPET) studies. The results suggest that both tracers do not present a clear preferential distribution in tissues rich in PBR, probably because of their molecular dimensions, which may hamper both the intracellular diffusion toward PBR and the interaction with the binding site.

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“…Besides, exposure to cigarette smoke (the main cause of COPD) altered TSPO expression, which leads to lung cancerization . Although lung disease shows an intrapulmonary macrophage overexpression that directly relates to TSPO expression, the PET imaging of inflammatory lung disorders in human demonstrates a reduced uptake due to diverse phenotypic macrophages. , However, [ 11 C]-PK11195 binding declines according to disease burden in fibrosing alveolitis, owing to systemic sclerosis (FASSc) patients and can be utilized to initiate immunosuppressive treatment. Owing to a few limitations, (multicellular TSPO expression in human lungs, diverse radioligand uptake, and overlap in patients and control) TSPO is not a true biomarker for lung disease diagnosis …”

Section: Inflammatory Lung Diseasesmentioning

confidence: 99%

Mapping of Translocator Protein (18 kDa) in Peripheral Sterile Inflammatory Disease and Cancer through PET Imaging

Adhikari

Singh

Mahar³

et al. 2021

Mol. Pharmaceutics

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Positron emission tomography (PET) imaging of the translocator 18 kDa protein (TSPO) with radioligands has become an effective means of research in peripheral inflammatory conditions that occur in many diseases and cancers. The peripheral sterile inflammatory diseases (PSIDs) are associated with a diverse group of disorders that comprises numerous enduring insults including the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system. TSPO has recently been introduced as a potential biomarker for peripheral sterile inflammatory diseases (PSIDs). The major critical issue related to PSIDs is its timely characterization and localization of inflammatory foci for proper therapy of patients. As an alternative to metabolic imaging, protein imaging expressed on immune cells after activation is of great importance. The five transmembrane domain translocator protein-18 kDa (TSPO) is upregulated on the mitochondrial cell surface of macrophages during inflammation, serving as a potential ligand for PET tracers. Additionally, the overexpressed TSPO protein has been positively correlated with various tumor malignancies. In view of the association of escalated TSPO expression in both disease conditions, it is an immensely important biomarker for PET imaging in oncology and PSIDs. In this review, we summarize the most outstanding advances on TSPO-targeted PSIDs and cancer in the development of TSPO ligands as a potential diagnostic tool, specifically discussing the last five years.

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Lung Tissue Mitochondrial Benzodiazepine Receptors Increase in a Model of Pulmonary Inflammation

Cited by 8 publications

References 27 publications

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs

Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs

Synthesis and Biological Characterization of Novel 2-Quinolinecarboxamide Ligands of the Peripheral Benzodiazepine Receptors Bearing Technetium-99m or Rhenium

Mapping of Translocator Protein (18 kDa) in Peripheral Sterile Inflammatory Disease and Cancer through PET Imaging

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