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PubMed1978

The interaction of iopanoic and iophenoxic acids with human serum albumin.

Iopanoic and iophenoxic acids are strongly bound to human serum albumin, as revealed from ultracentrifugation experiments. About two or three high affinity binding sites were found for both drugs. Within the concentration range investigated iopanoic acid is stronglier bound than iophenoxic acid. The binding to only one of the high affinity binding sites produces extrinsic Cotton effects. Further saturation of the high affinity binding sites decreases the extrinsic Cotton effects, possibly due to a binding induced change of the protein conformation.

Binding Sites↗

PubMed1981

Conventional oral cholecystography versus single-visit oral cholecystography.

The conventional manner of preparing ambulatory patients for oral cholecystography with six tablets of iopanoic acid yields results which are essentially equal to those obtained by single-visit oral cholecystography (two-day preparation with 12 tablets of iopanoic acid). Also, it is more convenient for patients and referring physicians. The conventional method of preparation is recommended for hospitalized patients as well.

Administration, Oral↗

PubMed1987

Characterization of type-II thyroxine 5'-deiodinase activity in rat Harderian gland.

Thyroxine 5'-deiodinase activity was studied in male rat Harderian gland homogenates. The reaction rate was proportional to the tissue content in the homogenate and dependent on pH, with an optimum pH of 7.0, and temperature, between 4-37 degrees C. 5'-deiodinase activity was increased by dithiothreitol (DTT) in a dose-dependent manner, and inhibited moderately by propylthiouracil (PTU) and strongly by iopanoic acid (IA). Thyroidectomy enhanced the enzymatic activity (30-fold above the control value) but this increase is totally prevented by the in vivo iopanoic acid treatment. Thyroxine 5'-deiodinase activity was also dependent on T4 concentration (Km = 3.3 nM; Vmax = 10 fmol 125I-released/mg protein/h) and exhibited a nyctohemeral rhythmicity with a maximal activity at 03.00 h (4-fold above basal values) and minimal activity between 12.00-21.00 h.

Animals↗

PubMed1981

Optimal perfusion rate determined for in situ intestinal absorption studies in rats.

Iopanoic acid was used as a model compound to study the effect of the intestinal perfusion rate on the mean absorption clearance. Absorption of iopanoic acid followed first-order kinetics, with a first-order absorption rate constant (ka) linearly dependent on the dry intestinal weight. An absorption clearance--time plot revealed three phases. Phase I represented an equilibration phase, Phase II was a uniform phase, and Phase III was a physiological deterioration of the animal under prolonged anesthesia. The variability in the observations during Phase II of the absorptive clearance--time profiles was assessed statistically, and the minimum occurred at 9.9 microliters/sec (0.594 ml/min). The relation between the coefficient of variance (CV) and the perfusion rate is given by CV = (-5.52 X 10(-5)Q3 + (2.78 X 10(-3)Q2 - (3.87 X 10(-2)Q + 0.243, where Q is the perfusion rate through the intestinal lumen. These studies demonstrate that an optimal flow rate exists for minimizing the variability in in situ absorption studies. The dependency of the absorption clearance on the intestinal perfusion rate appears to conform to the convective diffusion model.

Animals↗

PubMed1990

Inhibition of 5'-deiodination of thyroxine suppresses the cold-induced increase in brown adipose tissue messenger ribonucleic acid for mitochondrial uncoupling protein without influencing lipoprotein lipase activity.

Young adult male and female Djungarian hamsters were exposed to ambient temperatures of 23 or 0 C for 12 h; half of the animals in each group were treated with iopanoic acid to suppress the peripheral conversion of T4 to the thermotropically active thyroid hormone T3 by the enzyme 5'-deiodinase (5'D). Brown adipose tissue (BAT) mRNA for uncoupling protein (UCP), BAT lipoprotein lipase (LPL) activity, and 5'D activity were measured at the conclusion of the study. A temperature of 0 C produced large rises in 5'D and LPL activities and a similar large increase in UCP mRNA within the 12-h exposure period. When 5'D activity was inhibited with iopanoic acid, mRNA for UCP was reduced, while LPL activity was unaffected. The results show that the optimal production of mRNA for BAT UCP depends on the availability of T3; however, T3 is not required for the cold-induced activation of LPL activity in BAT.

Adipose Tissue, Brown↗

PubMed1988

Evidence that thyroxine inhibits either basal or TRH-induced TSH secretion only after conversion to triiodothyronine.

When TRH was administered every 15 min for 2 hr in euthyroid rats, equivalent modestly supraphysiologic doses of either T4 or T3 suppressed TRH-induced TSH secretion after 45 min. Pretreatment with iopanoic acid blocked the ability of T4 but not of T3 to suppress TRH-induced TSH secretion 2 hr after administration of the respective thyroid hormone. Pretreatment with iopanoic acid also blocked the ability of T4, but not of T3, to depress the elevated basal plasma TSH concentration of hypothyroid rats within 2 hr. Propylthiouracil did not significantly inhibit the ability of T4 to depress TRH-induced TSH secretion and only slightly depressed the ability of T4 to reduce the elevated plasma TSH of hypothyroid rats. Our data support the concept that although equivalent physiologic doses of T4 or T3 inhibit basal or TRH-induced TSH secretion equally rapidly, TSH inhibition produced by T4 is probably dependent on its rapid conversion to T3, either within the pituitary or peripherally. T3 thus seems to be exerting almost all the negative feedback effects on TSH secretion under the conditions of our experiments.

Animals↗

PubMed1998

Thyroxine 5'-deiodination mediates norepinephrine-induced lipogenesis in dispersed brown adipocytes.

In euthyroid rats, maximal sympathetic nervous system stimulation (e.g. during cold exposure) results in a 3- to 4-fold increase in brown adipose tissue lipogenesis, a response that is blunted in hypothyroid rats. To further investigate this phenomenon, the role of local type II 5'-deiodinase (5'-DII) was studied in freshly isolated brown adipocytes. In a typical experiment, 1.5 x 10(6) cells were incubated for up to 48 h in a water-saturated 5% CO2-95% O2 atmosphere. After incubation with medium alone or with different concentrations of T4, T3, and/or norepinephrine (NE), lipogenesis was studied by measuring 1) the rate of fatty acid synthesis as reflected by 3H2O incorporation into lipids and 2) the activity of key rate-limiting enzymes, i.e. acetyl coenzyme A carboxylase and malic enzyme, and the results are reported in terms of DNA content per tube. Lipogenesis decreased progressively over time (approximately 40%) when no additions were made to the incubation medium. T4 or T3 partially prevented that inhibition at physiological concentrations (65 x 10[-9] and 0.77 x 10[-9] M, respectively), whereas a receptor-saturating concentration of T3, (154 x 10[-9] M) doubled the lipogenesis rate. The addition of 10(-6) M NE inhibited lipogenesis acutely (approximately 50% by 12 h) and was followed by a progressive stimulation that reached approximately 2-fold by 48 h, but only in the presence of T4. Furthermore, NE did not attenuate T3 (154 x 10[-9] M)-induced lipogenesis. Both the inhibition and the stimulation of lipogenesis caused by NE showed a strong dose-response relationship within the range of 10(-11)-10(-5) M. The role of local 5'-DII was further tested by incubating brown adipocytes with 10(-6) M NE and T4 (65 x 10[-9] M) in the presence of 100 microM iopanoic acid, a potent inhibitor of 5'-DII. Although iopanoic acid did not affect the T3 stimulation of lipogenesis, it did block the approximately 2-fold stimulation of lipogenesis triggered by NE in the presence of T4, confirming the mediation of 5'-DII in this process. In conclusion, lipogenesis in brown adipose tissue is under complex hormonal control, with key roles played by NE, thyroid hormones, and local 5'-DII. As in other tissues, NE-generated signals acutely (12 h) inhibited lipogenesis. However, the presence of the 5'-DII generated enough T3 to stimulate lipogenesis and gradually reverse the short-lived NE-induced inhibition, leading to the 2- to 3-fold response observed at later time points.

Adipocytes↗

PubMed1985

Modulatory effect of thyroid hormones on uptake of phosphate and other solutes across luminal brush border membrane of kidney cortex.

The mechanism whereby thyroid hormones modulate the transport properties of luminal brush border membrane (BBM) of renal proximal tubules was studied in thyroparathyroidectomized rats. Administration of both T4 and T3 increased BBM capacity for Na+ gradient-dependent uptake of phosphate (Pi) by BBM vesicles (BBMV). This effect of thyroid hormones was present in thyroparathyroidectomized and hypophysectomized rats, and it was not blocked by a saturating dose of propranolol. The stimulatory effect of T3 and T4 on BBM transport of Pi was dose dependent in the range of 5.2-520 nmol/100 g BW. Pretreatment of rats with inhibitors of 5'-monodeiodinase (5'-DI), iopanoic acid or ipodate, prevented the increase in serum T3 in rats injected with T4, but it did not diminish the increase in BBM transport of Pi. Administration of iopanoic acid and ipodate also prevented a 5-fold increase in 5'-DI activity in renal cortical tissue elicited by T4 administration. Treatment with T3 resulted in an increase of Pi transport across BBM from kidneys of rats subjected to dietary Pi deprivation due either to total fasting or to feeding of a low Pi diet. Further, T3 administration enhanced amiloride-sensitive Na+-H+ countertransport across BBM, but the uptake of 22Na+ by BBMV in the absence of pH gradient was not changed. The Na+ gradient-dependent uptake of L-[3H]proline by BBMV was slightly decreased, but the uptake of [14C]citrate was not changed in response to T3. Administration of T3 increased Pi transport in BBMV prepared from juxtamedullary cortex, but not in BBMV from superficial cortex. Conversely, the rate of Na+-H+ countertransport was enhanced, and the enzymatic activity of alkaline phosphatase was decreased in BBMV from superficial cortex; no changes in these parameters were found in BBMV from juxtamedullary cortex. Our results indicate that the stimulatory effect of administered T3 and/or T4 on renal BBM transport of Pi is distinct from the modulatory effect of dietary Pi intake and is not secondary to the beta-effect of catecholamines or to altered secretion of GH. Both T3 and T4 elicit the increase in BBM transport of Pi in a similar manner; T4 is effective even after profound inhibition of in vivo conversion of T4 to T3 by potent 5'-DI inhibitors. Administration of T3 stimulates Na+ gradient-dependent Pi uptake only in BBMV prepared from the juxtamedullary zone, and it stimulates the H+-Na+ countertransport only in BBMV from the outer cortical zone. These findings indicate that thyroid hormones modulate the two distinct transport functions of BBM derived from two different populations of renal proximal tubules.

Animals↗

PubMed1975

Oral cholecystography: osmotic activity of iopanoic glucuronide in bile.

The cholecystographic agent iopanoic acid (Telepaque) is excreted in high concentrations in the bile as the glucuronide, but produces little or no choleresis. In order to determine the osmotic characteristics of the excretory product, bile was collected from treated and untreated anesthetized dogs and the major solute concentrations and biliary osmolality were determined. After iopanoic acid, there was no change in biliary osmolality or in chloride or bicarbonate concentration. However, the calculated osmolality exceeded the measured osmolality to a significant degree. The data suggest that iopanoic glucuronide, like bile salts, is osmotically inactive because of micelle formation. From physiological considerations, low osmotic activity of the excreted contrast agent might enhance radiographic quality.

Administration, Oral↗

PubMed2004

Oral contrast-enhanced CT cholangiography--an initial experience.

OBJECTIVE: To describe our experience of CT (Computed tomographic) Cholangiography examination for detection of choledocholithiasis at the Aga Khan University Hospital (AKUH) Karachi Pakistan. METHODS: Seven patients underwent helical CT cholangiography for suspected choledocholithiasis. Iopanoic acid (6 grams) was administered orally 8-12 hours before acquisition of a helical CT cholangiogram. Three-dimensional reconstructions and curved multiplanar reformations were generated from a set of axial source images. RESULTS: Our patients had no adverse reactions to iopanoic acid. The degree of biliary opacification was sufficient to perform three-dimensional and curved planar reformations in 5 patients. In two patients, the biliary tree was not opacified. Both of these studies were considered failures. Findings on CT cholangiography in the remaining 5 patients were the following: cholelithiasis with normal bile duct (n=2), choledocholithiasis (n=1), stone in gallbladder remnant with long cystic duct (n=1) and infiltrating adenocarcinoma of the gallbladder (n=1). CONCLUSION: Spiral CT cholangiography is a safe, non-invasive, and cost effective alternative test and, in a carefully selected patient population can play a role in the diagnostic work-up of patients with suspected choledocholithiasis.

Administration, Oral↗

PubMed1984

Iodothyronine 5'-deiodinase in rat kidney microsomes. Kinetic behavior at low substrate concentrations.

The thiol-activated enzymatic outer-ring monodeiodination of iodothyronines by rat kidney microsomes at low (nanomolar) substrate concentrations shows an apparently sequential reaction mechanism and is further characterized by insensitivity to inhibition by dicoumarol, a moderate sensitivity to inhibition by propylthiouracil (Ki = 100 microM) and iopanoic acid (Ki = 0.9 mM), responsiveness to 5 mM glutathione (GSH), and a thermal activation profile that is concave downward with a Td of approximately 20 degrees C. In contrast, the activity at high (micromolar) substrate concentrations shows a ping-pong reaction mechanism, is inhibited by micromolar concentrations of propylthiouracil, iopanoic acid and dicoumarol, is unresponsive to 5 mM GSH, and shows a concave upward thermal activation profile. Analysis of the microsomal deiodinase reaction over a wide range of 3,3',5'-triiodothyronine (rT3) concentrations (0.1 nM to 10 microM) suggested the presence of two enzymatic activities, with apparent Michaelis constants (Km) of 0.5 microM and 2.5 nM. Lineweaver-Burk plots of reaction velocities at nanomolar substrate concentrations in presence of 100 microM propylthiouracil also revealed an operationally distinct enzymatic activity with Km's of 2.5 and 0.63 nM and maximum velocities (Vmax's) of 16 and 0.58 pmol/mg protein per h for rT3 and thyroxine (T4), respectively. These findings are consistent with the presence of a low Km iodothyronine 5'-deiodinase in rat kidney microsomes distinct from the well characterized high Km enzyme and suggest that at circulating levels of free T4 the postulated low Km enzyme could be physiologically important.

Animals↗

PubMed1980

Phenolic and tyrosyl ring deiodination of iodothyronines in rat brain homogenates.

Conversion of thyroxine (T(4)) to 3,5,3'-triiodothyronine (T(3)) in rat brain has recently been shown in in vivo studies. This process contributes a substantial fraction of endogenous nuclear T(3) in the rat cerebral cortex and cerebellum. Production of T(4) metabolites besides T(3) in the brain has also been suggested. To determine the nature of these reactions, we studied metabolism of 0.2-1.0 nM [(125)I]T(4) and 0.1-0.3 nM [(131)I]T(3) in whole homogenates and subcellular fractions of rat cerebral cortex and cerebellum. Dithiothreitol (DTT) was required for detectable metabolic reactions: 100 mM DTT was routinely used. Ethanol extracts of incubation mixtures were analyzed by paper chromatography in t-amyl alcohol:hexane:ammonia and in 1-butanol:acetic acid. Rates of production of iodothyronines from T(4) and T(3) were greater at pH 7.5 than at 6.4 or 8.6 and greater at 37 degrees C than at 22 degrees or 4 degrees C. Lowering the pH, reducing the protein or DTT concentrations, and preheating homogenates to 100 degrees C all increased excess I(-) production but reduced iodothyronine production. In cerebral cortical homogenates from normal rats, products of T(4) degradation were as follows (percent added T(4)+/-SEM in nine experiments): T(3), 1.9+/-0.5%; 3,3',5'-triiodothyronine (rT(3)), 34.0+/-2.4%; 3,3'-diiodothyronine (3,3'-T(2)), 5.8+/-1.6%; 3'-iodothyronine (3'-T(1)), </=2.5%; and excess I(-), 4.7+/-1.2%. In the same experiments, products of T(3) degradation were 3,3'-T(2), 63.3+/-5.5%, and 3'-T(1), 12.6+/-1.4%. Cerebral cortical homogenates from hyperthyroid rats and normals were similar in regard to T(4) to T(3) deiodination. In contrast, in cerebral cortical homogenates from hypothyroid rats, phenolic ring deiodination rates were increased and tyrosyl ring deiodination rates were decreased compared with normals.T(4) to T(3) conversion rates in cerebellar homogenates were greater than rates in cerebral cortical homogenates from the same normal rats and less than rates in cerebellar homogenates from hypothyroid rats. T(4) and T(3) tyrosyl ring deiodination rates were greatly diminished in cerebellar homogenates compared with cerebral cortical homogenates in normal and hypothyroid rats. High-speed (1,000-160,000 g) pellets from cerebral cortical homogenates were enriched in phenolic and tyrosyl ring deiodinating activities relative to cytosol. Fractional conversion of T(4) to T(3) was inhibited by T(4), iopanoic acid, and rT(3), but not by T(3). Tyrosyl ring deiodination reactions were inhibited by T(3), T(4), and iopanoic acid, but not by rT(3). These studies demonstrate separate phenolic and tyrosyl ring iodothyronine deiodinase enzymes in rat brain. The brain phenolic ring deiodinase serves in vivo as a T(4) 5'-deiodinase and closely resembles anterior pituitary T(4) 5'-deiodinase in physiological and biochemical characteristics. The physiological significance of the tyrosyl ring iodothyronine deiodinase enzyme is unclear; it shares several properties with rat hepatic T(4) 5-deiodinase.

Animals↗

PubMedDate not supplied

[Acute poisoning with thyroxine in children].

Two girls aged 5 and 14 years were admitted to hospital after ingestion of L-thyroxine in estimated doses of 72 micrograms.kg and 118 micrograms.kg in the preceding 4 and 8 hours, respectively. Both had high serum T4 (19 and 20 micrograms/dl) and were asymptomatic at the time of admission and both were treated with Iopanoic acid 3 g orally every 72 hours, in order to block the conversion of T4 into T3. Serum levels of T4 were still elevated for up to ten days (8 and 16 micrograms/dl, respectively at day 10), but serum levels of T3 came down to 60 micrograms/dl within the first 48 hours of treatment in both cases. It should be taken into account that these patients may be initially asymptomatic and that symptoms may appear even later than 24 hours after the ingestion, so they should be admitted and treated at hospital. Iopanoic acid has been proved to be a treatment of choice in order to block the conversion of T4 into T3.

Administration, Oral↗

PubMed1992

Amiodarone decreases cardiac beta-adrenoceptors through an antagonistic effect on 3,5,3' triiodothyronine.

Because surprising similarities exist between the cardiac effects of amiodarone and those observed during hypothyroidism, we tested three different mechanisms of action in rats to determine whether amiodarone might act by inducing a tissular hypothyroidism: (a) a decrease in thyroid secretion, (b) an inhibiting effect on the conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3), and (c) a direct antagonistic effect on the cellular action of T3. Five groups of rats, treated orally for 7 or 13 days, were studied: I, control (0.5 ml saline for 7 or 13 days, n = 14); II, amiodarone (50 mg/kg for 7 days, n = 5); III, iopanoic acid (100 mg/kg for 13 days, n = 7); IV, control + T3 (0.5 ml saline for 13 days and 0.5 mg/kg T3 for the last 6 days, n = 5); V, amiodarone + T3 (amiodarone 50 mg/kg for 13 days and 0.5 mg/kg T3 for the last 6 days, n = 5). Cardiac beta-adrenoceptor density (CBARD) and heart rate (HR) were the two endpoint parameters investigated. Thyroid status was evaluated by serum thyrotropin (TSH), T4, T3, rT3 concentrations and liver type I 5'-deiodinase (5'D-I) activity. Amiodarone (group II) decreased CBARD (-22%, p less than 0.05) without altering thyroid secretion and T3 serum level, whereas 5'D-I was strongly inhibited (-90%, p less than 0.01). Iopanoic acid had no effect on CBARD and HR, but deeply inhibited 5'D-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗

PubMed2002

Are the effects of T3 on resting metabolic rate in euthyroid rats entirely caused by T3 itself?

Because we previously reported that T3 and 3,5-diiodo-L-thyronine (3,5-T2) both increase resting metabolic rate (RMR), 3,5-T2 could be another thyroidal regulator of energy metabolism. This effect of 3,5-T2 is evident in rats made hypothyroid by propylthiouracil and iopanoic acid, not in normal euthyroid (N) rats. Possibly, under euthyroid conditions, active 3,5-T2 may need to be formed intracellularly from a precursor such as T3. We tested this hypothesis by giving a single injection of T3 to N rats and comparing the time course of the variations in RMR with those of the changes in the serum and hepatic levels of 3,5-T2. Acute injection had an evident effect on RMR, 25 h earlier, in N rats than in rats made hypothyroid by propylthiouracil and iopanoic acid, maximal values (+40%) being reached in the former at 24-26 h. In N rats, the simultaneous injection of actinomycin D with the T3 inhibited the late part of the effect (after 24 h) more strongly than the early part (14-24 h). In serum and liver, 3,5-T2 levels were increased significantly at 12-24 h after T3 injection into N rats, a time at which RMR was rising rapidly to peak. These results seem to indicate that when T3 is injected into N animals, not all the effects on RMR are attributable to T3 itself, the early effect presumably being largely because of its in vivo deiodination to 3,5-T2. Because the effects of T3 and 3,5-T2 are additive, in N rats, the two iodothyronines probably cooperate in vivo to determine the total metabolic rate.

Animals↗

PubMedDate not supplied

Changes in bile flow and composition induced by radiographic contrast materials.

The hepatic excretion of radiographic contrast materials has a major impact on the composition and volume of bile. One obvious effect is the presence of the contrast agent in bile at a concentration that is determined by the rate of hepatic excretion, the rate of basal bile flow, and the rate of bile flow induced by the biliary excretion of the contrast agent. The magnitude of the choleretic response associated with the biliary transfer of contrast materials varies over a wide range. Iopanoic acid does not increase bile flow, whole RCK-136, an experimental contrast material that is similar to iopanoic acid chemically (both are triiodophenyl alkanoates), is a potent choleretic, generating 44 microliter of bile for each mumol excreted into bile. In distinction, the contrast materials in another chemical class, the dimers of triiodobenzoic acid, increase bile flow, but over a narrow range (20-25 microliter/mumol). The changes in bile flow and composition accompanying the administration of iodoxamate, one of the compounds of the dimer type, were compared to the choleresis induced by taurocholate. The additional bile flow was canalicular in origin in both instances, but the electrolyte composition of the bile was different. Bicarbonate concentration in the iodoxamate-induced increment of bile was nearly twice the concentration of bicarbonate in bile stimulated by taurocholate (52.3 and 25.3 mEq/1, respectively). This suggests a canalicular mechanism for iodoxamate-stimulated bicarbonate entry into the bile. The characteristics of bile induced by iodoxamate were also compared to bile associated with a variety of other choleretic agents, including diethyl maleate, DBcAMP, SC2644, and secretin. Only SC2644 stimulated canalicular bile flow with a high bicarbonate concentration similar to iodoxamate.

Animals↗

PubMed1992

Diphenylhydantoin stimulates the intrapituitary conversion of thyroxine to triiodothyronine in the rat.

Treatment of normal rats with diphenylhydantoin (DPH) decreases serum thyroxine (T4) and triiodothyronine (T3) levels without the anticipated rise in serum thyrotropin (TSH). The present work has studied the intrapituitary conversion of T4 to T3 in male Wistar rats, 200-250 g body weight (BW), treated with DPH 5 mg/100 g BW/day for 8 days. A tracer dose of 3',5'-[125I]T4 (150 microCi) was injected intravenously, and 2 h later hypophyses were removed and homogenized individually at 4 degrees C in ice-cold PBS buffer (pH 7.4). T4 and T3 were extracted in 400 microliters n-butanol:2 N HCl (9:1) and chromatographed in tertiary amyl alcohol:hexane: 1 N ammonia (5:1:6). In 11 untreated control rats, [125I]T3 generated from [125I]T4 deiodination was 35 +/- 6% and intact [125I]T4 was 49 +/- 9% of total chromatographic radioactivity. In 11 DPH-treated rats [125I]T3 increased (p < 0.001) and [125I]T4 decreased (p < 0.02). The DPH effect was blocked in rats treated for 2 days with iopanoic acid 10 mg/100 g BW, though blocking was not seen in rats treated with half the dose of iopanoic acid. In normal rats receiving supplemental doses of T4 (2 micrograms/100 g BW/day for 8 days), DPH similarly increased pituitary 5'-deiodination. Administration of propylthiouracil (PTU) to T4-supplemented rats had no effect on pituitary 5'-deiodination of T4, whereas the addition of DPH to PTU treatment increased [125I]T3 production (p < 0.01). Serum T4 (p < 0.001) and T3 (p < 0.01) were decreased after DPH therapy, while serum and pituitary TSH were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

The effects of radiographic contrast agents and other compounds on the nuclear binding of L-[125I]triiodothyronine in dispersed human skin fibroblasts.

Using a dispersed intact cell assay system, we screened a number of compounds for their ability to compete for nuclear binding of L-[125I]T3 in cultured human skin fibroblasts incubated for 90 min at 37 degrees C. T3 inhibited nuclear [125I]T3 binding by 50% at a concentration of 3.4 +/- 0.3 (+/- SE) X 10(-10) M. 3,5-Dimethyl-3'-isopropyl-thyronine, a nonhalogenated thyroid hormone agonist, had an affinity for the nuclear thyroid hormone receptor (4.4 X 10(-9) M, as judged by 50% inhibition of nuclear [125I]T3 binding) that correlates well with its thyromimetic potency. Of several radiographic contrast agents and other compounds tested (iodipamide, iopanoic acid, sodium ipodate, sodium diatrizoate, sodium tyropanoate, diphenylhydantoin, carbamazepine, amiodarone hydrochloride, propylthiouracil, propranolol, and potassium iodide), only sodium ipodate (Oragrafin) and iopanoic acid (Telepaque) interfered with nuclear [125I]T3 binding, with 50% inhibition at 5 X 10(-5) and 1.8 X 10(-4) M, respectively. Interestingly, diphenylhydantoin and amiodarone, two compounds previously thought to interact with thyroid hormone receptors, did not impair fibroblast nuclear [125I]T3 binding at concentrations up to 10(-3) M. We conclude that this in vitro assay system with intact human cells is useful in evaluating the nuclear T3 receptor affinity of compounds that affect thyroid hormone action or metabolism. These studies more closely approximate in vivo conditions and, therefore, provide information not obtainable by studies with isolated nuclei or nuclear extracts.

Binding, Competitive↗