Abstract
When rats were dosed with 14 μg/kg 3H-isoproterenol, 3H-radioactivity was measurable in the liver until 48 h. This amount was not different in livers of animals which have been pretreated with diethyl maleate.
After exhaustive extraction, a significant amount of 3H-radioactivity from isoproterenol could be detected in the proteins of total liver (homogenate), of cytosol and of microsomes. In the cytosol fraction of diethyl maleate pretreated animals twice the amount of isoproterenol-radioactivity was found in the extracted proteins compared to controls. In the microsomal fraction there was no difference between diethyl maleate pretreated and control animals in the amount of radioactivity incorporated into proteins.
In all fractions the radioactivity measurable in the extracted proteins declined with a half life time of about 24 h.
The in vivo results on covalent binding of isoproterenol are compared to the irreversible protein binding of ethinyloestradiol in vivo. Quantitatively, these in vivo data are compared to the results on irreversible protein binding obtained during incubations of isoproterenol or ethinyloestradiol with rat liver microsomes.
Zusammenfassung
Wenn Ratten mit 14 μg/kg 3H-Isoproterenol behandelt wurden, konnte bis 48 h danach in der Leber 3H-Radioaktivität gemessen werden. Diese Menge war nicht unterschiedlich in Lebern von Tieren, welche mit Diäthylmaleat vorbehandelt waren. Nach erschöpfender Extraktion konnte eine beträchtliche Menge an 3H-Radioaktivität aus Isoproterenol in den Proteinen von Gesamtleber (Homogenat), Cytosol und von Mikrosomen gefunden werden. In der Cytosolfraktion von Diäthylmaleat vorbehandelten Tieren wurde die zweifache Menge von Isoproterenol-Radioaktivität in den extrahierten Proteinen gefunden, im Vergleich zu Kontrollen. In der mikrosomalen Fraktion gab es keinen Unterschied bei der Radioaktivitätsmenge, die in Proteine eingebaut war.
In allen Fraktionen nahm die Radioaktivität, die in den extrahierten Proteinen meßbar war, mit einer Halbwertszeit von etwa 24 h ab.
Die in vivo-Ergebnisse über kovalente Proteinbindung von Isoproterenol werden verglichen mit der irreversiblen Proteinbindung von Äthinylöstradiol in vivo. Quantitativ werden diese in vivo-Befunde mit den Resultaten zur irreversiblen Proteinbindung verglichen, die während Inkubationen von Isoproterenol oder Äthinylöstradiol mit Rattenlebermikrosomen erhalten wurden.
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Remmer, H., Scheulen, M., Kappus, H. et al. The significance of covalent binding of catechols to proteins in vivo. Arch. Toxicol. 39, 31–39 (1977). https://doi.org/10.1007/BF00343273
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DOI: https://doi.org/10.1007/BF00343273