Rats were injected with [125I]L-thyroxine (T4) ip 16 h before the experiment and samples of blood were frequently taken from polyethylene tubing inserted into the femoral artery in anaesthetized and heparin injected animals, isovolaemia being maintained. In each sample of plasma T4 counts per ml were estimated with the aid of paper chromatography. Rapid decrease of circulating T4 level was found at 20 min after iv injection of various compounds (thiocyanate, iodide, fluoroborate, theophylline and salicylate) and a dose-response relationship was established between such a decrease and the administered dose of salicylate (5\p=n-\160 mg/400 g b. w.). A similar decrease was observed at 60 min after ip injection of some general anaesthetics (thio-, pento-and allo-barbiturate, urethane) or tranquilizers (Innovar-Vet\s=r\).Finally, an increase of T4 fractional disposal rate was found between 120 and 480 min after the administration of some of the above mentioned anaesthetics and this effect was abolished by the administration of thiocyanate. It was concluded that there are two different effects of drugs on the circulating T4 level: 1. the immediate effect resulting apparently from a decreased plasma protein binding; 2. the prolonged effect which presumably results from the increased turnover of T4 by peripheral tissues, the metabolic basis of which remains unexplained.
Polyethylene tubes were inserted into the bile duct and femoral vein of rats under pentobarbital anaesthesia and bile was collected for three 2-h periods. After the first (control) period the animals were infused intravenously at a rate of 1.2 ml/h with the following compounds: (1) 0.9% (w/v) NaCl (control group), (2) glucagon (1200 ng/h), (3) vasopressin (1200 ng/h) or (4) angiotensin II (600 ng/h). The concentrations of thyroxine (T4), tri-iodothyronine (T3) and reverse tri-iodothyronine (rT3) in the bile were estimated by radioimmunoassay. No significant differences between groups were found in the biliary excretion of T4 and T3, while the excretion of rT3 after the infusion of all the hormones used was significantly (P less than 0.001 at 2 to 4 h of the infusion) increased, no such increase being found in the controls. It may be concluded therefore that the administration of the above hormones resulted in some changes in iodothyronine metabolism in the liver. These may be explained by an inhibition of iodothyronine 5'-monodeiodination related to the glycogenolytic and gluconeogenetic effects of these hormones.
Biliary excretion of total (i.e. conjugated plus unconjugated) thyroxine (T4), 3,5,3'-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3), 3,5-diiodothyronine (3,5-T2), 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2) was measured with the aid of specific radioimmunoassay in 17 control rats and in 31 rats injected sodium salicylate i.v. (200 mg kg-1). The animals were anesthetized with pentobarbiturate and the samples of bile were taken in subsequent 2 h periods from a drained bile duct. In controls a gradual decrease of excretion of all compounds measured was found during 10 h observation period. In contrast, after salicylate injection a transient increase of total bile volume and of T4, T3 and 3,5-T2 excretion was observed followed by a remarkable decrease, while a multifold and prolonged increase of the excretion of rT3, 3,3'-T2 and 3',5'-T2 was found. These data suggest an acute and remarkable effect of salicylate on T4 deiodinating pathway in the liver.
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