Binding of radioactivity from (14C)thiourea to rat lung protein.
Binding of radioactivity from [14C]thiourea (TU) to rat lung protein was found to occur in vitro. Two binding sites are present. One possesses low affinity/high capacity while the other is characterized by high affinity/low capacity. In vitro binding of [14C]TU to lung protein can be antagonized by the presence of either unlabeled congeners (alpha-napthylthiourea or phenylthiourea) or thiol-containing compounds (cysteine, reduced glutathione). Conversely, depletion of lung-reduced glutathione by means of diethyl maleate administration results in elevated protein binding. Prior administration (24 hr) of a sublethal dose of TU (which renders tolerance to a subsequent lethal dose in vivo) results in a decrease in in vitro binding of radioactivity from [14C)TU to lung protein. In addition, immature rats, which are less sensitive to the edematogenic effect of TU, bind less radioactivity from [14C]TU to lung protein when the drug is administered in vivo. These results suggest a correlation between [14C]TU binding to lung protein and the pathophysiological effect of the drug in the lung.
Binding of radioactivity from (14C)thiourea to rat lung protein. Binding of radioactivity from [14C]thiourea (TU) to rat lung protein was found to occur in vitro. Two binding sites are present. One possesses low affinity/high capacity while the other is characterized by high affinity/low capacity. In vitro binding of [14C]TU to lung protein can be antagonized by the presence of either unlabeled congeners (alpha-napthylthiourea or phenylthiourea) or thiol-containing compounds (cysteine, reduced glutathione). Conversely, depletion of lung-reduced glutathione by means of diethyl maleate administration results in elevated protein binding. Prior administration (24 hr) of a sublethal dose of TU (which renders tolerance to a subsequent lethal dose in vivo) results in a decrease in in vitro binding of radioactivity from [14C)TU to lung protein. In addition, immature rats, which are less sensitive to the edematogenic effect of TU, bind less radioactivity from [14C]TU to lung protein when the drug is administered in vivo. These results suggest a correlation between [14C]TU binding to lung protein and the pathophysiological effect of the drug in the lung.