Lung tissue mitochondrial benzodiazepine receptors increase in a model of pulmonary inflammation.
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.
Audi
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Biomedical Engineering Department, Marquette University, Milwaukee, WI 53201-1881, USA. audis@marquette.edu
Dawson
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CA
Ahlf
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SB
Roerig
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D000818:Animals; D002250:Carbon Radioisotopes; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D005620:Freund's Adjuvant; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011817:Rabbits; D011963:Receptors, GABA-A / Q000502:physiology*
D002250:Carbon Radioisotopes; D004792:Enzyme Precursors; D011963:Receptors, GABA-A; D005620:Freund's Adjuvant; D053148:Caspase 3; D020169:Caspases; D003975:Diazepam