Development and Use of a Mathematical Two-Pool Model of Distribution and Metabolism of 3,3′,5-Triiodothyronine in a Recirculating Rat Liver Perfusion System: Albumin Does not Play a Role in Cellular Transport*

Docter, R.; Jong, Marion de; Hoek, H. J. Van Der; Krenning, E. P.; Hennemann, G

doi:10.1210/endo-126-1-451

Cited by 16 publications

(4 citation statements)

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“…134). Similar to the results in cultured rat hepatocytes, we found that, in addition to the energy state of the liver, the free hormone concentration in the perfusion medium determined the amount of hormone taken up by the intracellular compartment of the liver (135). Studies using livers from amiodarone-treated animals indicated that transport of T., but not of T3, was inhibited (136), in agreement with hepatocyte studies (47,55) showing that T. and T3 are transported differently across the liver plasma membrane.…”

Section: A Transport Into the Liversupporting

confidence: 85%

Thyroid hormone transporters

Friesema

Jansen

Visser

2005

Biochemical Society Transactions

106

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Thyroid hormone is important for development of various tissues, in particular brain, and for regulation of metabolic processes throughout life. The follicular cells of the thyroid gland produce predominantly T4 (thyroxine), but the biological activity of thyroid hormone is largely exerted by T3 (3,3',5-tri-iodothyronine). The deiodinases involved in T4-to-T3 conversion or T4 and T3 degradation, as well as the T3 receptors, are located intracellularly. Therefore the action and metabolism of thyroid hormone require transport of iodothyronines across the cell membrane via specific transporters. Recently, a number of transporters capable of cellular uptake of iodothyronines have been identified. The most specific transporters identified so far are OATP1C1 and MCT8, which appear to be involved in T4 transport across the blood-brain barrier, and in T3 transport into brain neurons, respectively. The MCT8 gene is located on human chromosome Xq13, and mutations in MCT8 are associated with X-linked severe psychomotor retardation and elevated serum T3 levels.

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Section: A Transport Into the Liversupporting

confidence: 85%

Thyroid hormone transporters

Friesema

Jansen

Visser

2005

Biochemical Society Transactions

106

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“…134). Similar to the results in cultured rat hepatocytes, we found that, in addition to the energy state of the liver, the free hormone concentration in the perfusion medium determined the amount of hormone taken up by the intracellular compartment of the liver (135). Studies using livers from amiodarone-treated animals indicated that transport of T 4 , but not of T 3 , was inhibited (136), in agreement with hepatocyte studies (47,55) showing that T 4 and T 3 are transported differently across the liver plasma membrane.…”

Section: A Transport Into the Liversupporting

confidence: 85%

Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability

et al. 2001

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Although it was originally believed that thyroid hormones enter target cells by passive diffusion, it is now clear that cellular uptake is effected by carrier-mediated processes. Two stereospecific binding sites for each T4 and T3 have been detected in cell membranes and on intact cells from humans and other species. The apparent Michaelis-Menten values of the high-affinity, low-capacity binding sites for T4 and T3 are in the nanomolar range, whereas the apparent Michaelis- Menten values of the low-affinity, high-capacity binding sites are usually in the lower micromolar range. Cellular uptake of T4 and T3 by the high-affinity sites is energy, temperature, and often Na+ dependent and represents the translocation of thyroid hormone over the plasma membrane. Uptake by the low-affinity sites is not dependent on energy, temperature, and Na+ and represents binding of thyroid hormone to proteins associated with the plasma membrane. In rat erythrocytes and hepatocytes, T3 plasma membrane carriers have been tentatively identified as proteins with apparent molecular masses of 52 and 55 kDa. In different cells, such as rat erythrocytes, pituitary cells, astrocytes, and mouse neuroblastoma cells, uptake of T4 and T3 appears to be mediated largely by system L or T amino acid transporters. Efflux of T3 from different cell types is saturable, but saturable efflux of T4 has not yet been demonstrated. Saturable uptake of T4 and T3 in the brain occurs both via the blood-brain barrier and the choroid plexus-cerebrospinal fluid barrier. Thyroid hormone uptake in the intact rat and human liver is ATP dependent and rate limiting for subsequent iodothyronine metabolism. In starvation and nonthyroidal illness in man, T4 uptake in the liver is decreased, resulting in lowered plasma T3 production. Inhibition of liver T4 uptake in these conditions is explained by liver ATP depletion and increased concentrations of circulating inhibitors, such as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, indoxyl sulfate, nonesterified fatty acids, and bilirubin. Recently, several organic anion transporters and L type amino acid transporters have been shown to facilitate plasma membrane transport of thyroid hormone. Future research should be directed to elucidate which of these and possible other transporters are of physiological significance, and how they are regulated at the molecular level.

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“…Livers of male Wistar rats (200-250 g) were isolated and perfused in a recirculating system at 37°C as described previously. [9]. The magnetically stirred perfusion medium used in all experiments was 150 ml KrebsRinger buffer (ll8mmol/1 NaC1, 5retool/1 KC1, 1.1 mmol/l MgSO 4, 2.5 mmol/1 CaC12, 1.2 mmol/1 KHzPO 4, and 25 mmol/1 NaHCO3) supplemented with 10 mM glucose and 1% BSA.…”

Section: Radiolabelling and Quality Control Of The Radiopharmaceuticalmentioning

confidence: 99%

Evaluation in vitro and in rats of161Tb-DTPA-octreotide, a somatostatin analogue with potential for intraoperative scanning and radiotherapy

et al. 1995

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The characteristics of terbium-161 diethylene triamine penta-acetic acid (DTPA) labelled octreotide with respect to specific binding to somatostatin (octreotide) receptors on rat brain cortex membranes, biological activity, uptake and excretion by isolated perfused rat livers and metabolism in vivo in normal and tumour-bearing rats were determined and compared to those of indium-111 DTPA-octreotide. The results of the binding studies demonstrate that 161Tb-DTPA-octreotide is a high-affinity radioligand for somatostatin receptors, with an affinity comparable to that of 111In-DTPA-octreotide. Rat growth hormone secretion inhibition experiments showed that 161Tb-DTPA-octreotide has a similar potency to 111In-DTPA-octreotide. 161Tb-DTPA-octreotide appeared to be taken up even less by the isolated perfused rat liver than 111In-DTPA-octreotide, as almost no tracer disappeared from the perfusion medium. Furthermore, hardly any radioactivity was found in the liver, and excretion into the bile was negligible. The biodistribution studies showed that for octreotide receptor-positive organs, such as pancreas and adrenals, uptake of 161Tb-DTPA-octreotide is lower then that of 111In-DTPA-octreotide. However, as the clearance from the blood of the former compound is faster than that of the latter, the tissue/blood ratio is higher in the case of 161Tb-DTPA-octreotide than with 111In-DTPA-octreotide. Furthermore, these studies demonstrated that the uptake of 161Tb-DTPA-octreotide by the renal tubular cells after glomerular filtration can be reduced by administration of lysine or sodium maleate. Increase in urine production before and during the experiment had no effect on the kidney uptake of 161Tb-DTPA-octreotide.(ABSTRACT TRUNCATED AT 250 WORDS)

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Development and Use of a Mathematical Two-Pool Model of Distribution and Metabolism of 3,3′,5-Triiodothyronine in a Recirculating Rat Liver Perfusion System: Albumin Does not Play a Role in Cellular Transport*

Cited by 16 publications

References 0 publications

Thyroid hormone transporters

Thyroid hormone transporters

Plasma Membrane Transport of Thyroid Hormones and Its Role in Thyroid Hormone Metabolism and Bioavailability

Evaluation in vitro and in rats of161Tb-DTPA-octreotide, a somatostatin analogue with potential for intraoperative scanning and radiotherapy

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