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The objective of this study was to investigate whether lung injury induced by intratracheal CEES exposure (2 mg\/kg body weight) causes desensitization of \u03b2\u2010ARs. The animals were sacrificed after 7 days and lungs were removed. Lung injury was established by measuring the leakage of iodinated\u2010bovine serum albumin ([<jats:sup>125<\/jats:sup>I]\u2010BSA) into lung tissue. Receptor\u2010binding characteristics were determined by measuring the binding of [<jats:sup>3<\/jats:sup>H] dihydroalprenolol ([<jats:sup>3<\/jats:sup>H] DHA) (0.5\u201324 nM) to membrane fraction in the presence and absence of<jats:sc>DLDL<\/jats:sc>\u2010propranolol (10 \u03bc M). Both high\u2010 and low\u2010affinity \u03b2\u2010ARs were identified in the lung. Binding capacity was significantly higher in low\u2010affinity site in both control and experimental groups. Although CEES exposure did not change<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>and<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>at the high\u2010affinity site, it significantly decreased both<jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub>and<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>at low affinity sites. A 20% decrease in \u03b2<jats:sub>2<\/jats:sub>\u2010AR mRNA level and a 60% decrease in membrane protein levels were observed in the experimental group. Furthermore, there was significantly less stimulation of adenylate cyclase activity by both cholera toxin and isoproterenol in the experimental group in comparison to the control group. Treatment of lungs with 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX), an inhibitor of phosphodiesterase (PDE) could not abolish the difference between the control group and the experimental group on the stimulation of the adenylate cyclase activity. Thus, our study indicates that CEES\u2010induced lung injury is associated with desensitization of \u03b2<jats:sub>2<\/jats:sub>\u2010AR. \u00a9 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:59\u201370, 2009; Published online in Wiley InterScience (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.interscience.wiley.com\">www.interscience.wiley.com<\/jats:ext-link>). 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