Related Experiment Video
Updated: Aug 4, 2026
Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke
Published on: February 12, 2015
Lung tissue mitochondrial benzodiazepine receptors increase in a model of pulmonary inflammation
S H Audi1, C A Dawson, S B Ahlf
1Biomedical Engineering Department, Marquette University, Milwaukee, WI 53201-1881, USA. audis@marquette.edu
Abstract:
Pulmonary inflammation induced in the rabbit lung by the intravenous injection of complete Freund's adjuvant (CFA) increases the lung uptake of 14C-diazepam from the pulmonary circulation. The objective of this study was to determine the extent to which mitochondrial (or peripheral) benzodiazepine receptors (mBRs) may contribute to this increased uptake. To this end, we measured the pulmonary venous effluent concentration versus time for 14C-diazepam following its injection into the pulmonary artery of isolated perfused normal and CFA inflamed lungs with and without an inhibitor (PK11195) of diazepam binding to mBRs. The results demonstrate that this model of pulmonary inflammation is associated with an increase in lung tissue mBR. Lung tissue caspase-3 activity was also measured as one index of lung inflammation, and we found that in inflamed lungs, there was an inverse correlation between mBR density and lung tissue capase-3 activity. This is consistent with observations in other organs and a role for mBRs in apoptotic elimination of inflammatory cells in the resolution of this inflammatory response. The results suggest the potential utility of mBR ligands for noninvasive detection and/or characterization of pulmonary inflammation, e.g., via nuclear medicine methods.
Insights
Pulmonary inflammation increases lung uptake of diazepam. Mitochondrial benzodiazepine receptors (mBRs) are implicated, suggesting potential for mBR ligands in detecting lung inflammation.
Area of Science:
- Pharmacology and Toxicology
- Respiratory Medicine
- Cell Biology
Background:
- Pulmonary inflammation, induced by Complete Freund's Adjuvant (CFA), enhances lung uptake of 14C-diazepam.
- Mitochondrial benzodiazepine receptors (mBRs) are implicated in various cellular processes, including inflammation.
Purpose of the Study:
- To investigate the contribution of mitochondrial benzodiazepine receptors (mBRs) to increased lung uptake of diazepam during pulmonary inflammation.
- To assess the density of mBRs and their correlation with inflammatory markers in an experimental model of lung inflammation.
Main Methods:
- Isolated perfused rabbit lungs (normal and CFA-inflamed) were used to measure 14C-diazepam pulmonary venous effluent.
- PK11195, an inhibitor of diazepam binding to mBRs, was administered to assess receptor involvement.
- Lung tissue caspase-3 activity was measured as an indicator of inflammation.
Main Results:
- Pulmonary inflammation significantly increased lung tissue mBR density.
- An inverse correlation was observed between mBR density and lung tissue caspase-3 activity in inflamed lungs.
- PK11195 partially inhibited diazepam uptake, confirming mBR involvement.
Conclusions:
- Mitochondrial benzodiazepine receptors play a role in the increased lung uptake of diazepam during pulmonary inflammation.
- Increased mBR density in inflamed lungs may be linked to the apoptotic elimination of inflammatory cells.
- mBR ligands show potential for noninvasive detection and characterization of pulmonary inflammation using nuclear medicine.
