Effect of different beta-blocking drugs and adrenaline on the conversion of thyroxine to triiodothyronine in isolated rat hepatocytes.
The in vitro effect of various selective and non-selective beta-blocking drugs and adrenaline on the conversion of thyroxine (T4) to triiodothyronine (T3) was studied in suspensions of isolated rat hepatocytes after 90 min of incubation. Compared with the untreated controls propranolol caused a dose-related inhibition of the T4 to T3 conversion in conc of 100, 200 and 400 microM. The other beta-blocking drugs studied, timolol, oxprenolol, atenolol and metoprolol, were without any effect on this in vitro conversion. Propranolol did not interfere with the cellular association of T4 or the degradation of T4 and T3. Adrenaline 200 microM caused a small decrease of T3 in the medium and a corresponding increase in the intracellular content of T3. The inhibitory effect of propranolol 200 microM was not antagonized by equimolar concentrations of adrenaline. Our study suggests that the inhibitory effect of propranolol on the conversion of T4 to T3 in hepatocytes is caused by a direct chemical effect of the drug unrelated to its beta-blocking and membrane stabilizing properties.
Aanderud
S
S
Aarbakke
J
J
Sundsfjord
J
J
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D004837:Epinephrine / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D014284:Triiodothyronine; D013974:Thyroxine; D004837:Epinephrine