Inhibition by propranolol of 3,5,3'-triiodothyronine formation from thyroxine in isolated rat renal tubules: an effect independent of beta-adrenergic blockade.
Recent studies in man have shown a decrease in serum L-T3 (T3) levels in subjects treated with DL-propranolol, but the mechanism of this effect is unknown. Isolated rat renal tubules were used to study the effect of propranolol and related drugs on the formation of T3 from L-T4 (T4). Racemic (DL) propranolol at 100 microM inhibited the net formation of T3 from T4 by 35% (P less than 0.01). The D- and L-isomers of propranolol were also potent in inhibiting T3 formation, but the beta-blockers atenolol and sotalol, which have no significant membrane-stabilizing activity, had no effect at similar concentrations. Quinidine inhibited T3 formation, with a dose-response curve which was similar over the concentrations studied to that of DL-propranolol. L-Epinephrine and L-isoproterenol had no effect on T3 formation, and equimolar amounts of L-isoproterenol did not prevent the inhibition of T3 formation by DL-propranolol. cAMP production was stimulated by 200 micro M L-isoproterenol, and this was blocked by an equimolar concentration of DL-propranolol but not of D-propranolol. It is concluded that DL-propranolol directly inhibits net T3 formation from T4 in this system by a direct membrane-stabilizing or quinidine-like action and not by specific beta-blockade.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D013015:Sotalol / Q000494:pharmacology; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000096:biosynthesis*
D000319:Adrenergic beta-Antagonists; D014284:Triiodothyronine; D001262:Atenolol; D011433:Propranolol; D013015:Sotalol; D000242:Cyclic AMP; D007545:Isoproterenol; D013974:Thyroxine; D004837:Epinephrine