The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells

1988 ◽  
Vol 119 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Motoyasu Saji ◽  
Osamu Isozaki ◽  
Toshio Tsushima ◽  
Mariko Arai ◽  
Megumi Miyakawa ◽  
...  
Keyword(s):  
Cell Growth ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Production ◽  
Iodide Uptake ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Camp Generation ◽  
Rat Thyroid ◽  
Sites Of Action

Abstract. The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10−6 mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.

A novel role for AMP-kinase in the regulation of the Na+/I−-symporter and iodide uptake in the rat thyroid gland

2011 ◽  
Vol 300 (6) ◽  
pp. C1291-C1297 ◽  
Author(s):  
Bruno M. Andrade ◽  
Renata L. Araujo ◽  
Robert L. S. Perry ◽  
Elaine C. L. Souza ◽  
Juliana M. Cazarin ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Dependent Manner ◽  
Amp Kinase ◽  
Iodide Uptake ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Compound C ◽  
Ampk Phosphorylation ◽  
Mrna Content ◽  
Rat Thyroid

The aim of this study was to investigate the role of AMP-kinase (AMPK) in the regulation of iodide uptake by the thyroid gland. Iodide uptake was assessed in PCCL3 follicular thyroid cells exposed to the AMPK agonist 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR), and also in rat thyroid glands 24 h after a single intraperitoneal injection of AICAR. In PCCL3 cells, AICAR-induced AMPK and acetyl-CoA carboxylase (ACC) phosphorylation decreased iodide uptake in a concentration-dependent manner, while the AMPK inhibitor compound C prevented this effect. In the thyroid gland of rats injected with AICAR, AMPK and ACC phosphorylation was increased and iodide uptake was reduced by ∼35%. Under conditions of increased AMPK phosphorylation/activation such as TSH deprivation or AICAR treatment, significant reductions in cellular Na+/I−-symporter (NIS) protein (∼41%) and mRNA content (∼65%) were observed. The transcriptional (actinomycin D) and translational (cycloheximide) inhibitors, as well as the AMPK inhibitor compound C prevented AICAR-induced reduction of NIS protein content in PCCL3 cells. The presence of TSH in the culture medium reduced AMPK phosphorylation in PCCL3 cells, while inhibition of protein kinase A (PKA) with H89 prevented this effect. Conversely, the adenylyl cyclase activator forskolin abolished the AMPK phosphorylation response induced by TSH withdrawal in PCCL3 cells. These findings demonstrate that TSH suppresses AMPK phosphorylation/activation in a cAMP-PKA-dependent manner. In summary, we provide novel evidence that AMPK is involved in the physiological regulation of iodide uptake, which is an essential step for the formation of thyroid hormones as well as for the regulation of thyroid function.

Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct

1994 ◽  
Vol 266 (5) ◽  
pp. F791-F796 ◽  
Author(s):  
R. M. Edwards ◽  
W. S. Spielman
Keyword(s):  
Receptor Agonist ◽  
Collecting Duct ◽  
Basolateral Membrane ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Accumulation ◽  
Concentration Dependent Manner ◽  
Cgs 21680 ◽  
Camp Generation ◽  
A1 Receptor

We examined the effects of adenosine and adenosine analogues on arginine vasopressin (AVP)-induced increases in osmotic water permeability (Pf; micron/s) and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat inner medullary collecting ducts (IMCDs). When added to the bath, the A1 receptor agonist N6-cyclohexyladenosine (CHA) produced a rapid and reversible inhibition of AVP-stimulated (10 pM) Pf (1,781 +/- 195 to 314 +/- 85 microns/s at 0.3 microM CHA; n = 9). The inhibitory effect of CHA was concentration dependent, with a 50% inhibitory concentration of 10 nM. The effect of CHA was inhibited by prior exposure of IMCDs to the A1 receptor antagonist 1,3-dipropylxanthine-8-cyclopentylxanthine (DP-CPX; 1 microM) or by preincubation with pertussis toxin. CHA had no effect on cAMP-induced increases in Pf. In addition to CHA, adenosine and the nonselective agonist 5'-(N-ethylcarboxamido)-adenosine (NECA) inhibited AVP-dependent Pf by > or = 70%, whereas the A2 receptor agonist CGS-21680 had no effect. Luminal adenosine (0.1 mM) had no effect on basal or AVP-stimulated Pf. CHA, NECA, and adenosine but not CGS-21680 inhibited AVP-stimulated cAMP accumulation in a concentration-dependent manner (50% inhibitory concentrations 0.1–300 nM). The inhibitory effect of CHA on AVP-stimulated cAMP accumulation was attenuated by DPCPX. We conclude that adenosine, acting at the basolateral membrane, inhibits AVP action in the IMCD via interaction with A1 receptors. The inhibition occurs proximal to cAMP generation and likely involves an inhibitory G protein.

Inhibitory action of somatostatin-14 on hormone-stimulated cyclic adenosine monophosphate induction in porcine granulosa and luteal cells

1992 ◽  
Vol 134 (2) ◽  
pp. 297-306 ◽  
Author(s):  
K. Rajkumar ◽  
D. E. Kerr ◽  
R. N. Kirkwood ◽  
B. Laarveld
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Luteal Cells ◽  
Camp Generation ◽  
Camp Induction ◽  
Camp Levels ◽  
Somatostatin 14

ABSTRACT Somatostatin-14 (SRIF-14) inhibited, in a concentration-dependent manner, LH- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) induction in porcine granulosa and luteal cells. The inhibitory effect of SRIF-14 on hormone-induced cAMP generation was more potent in porcine ovarian cells than in the GH-3 pituitary cell line. The inhibitory effect of SRIF-14 was impeded by neutralizing its biological activity with specific antiserum. Preincubation of luteal and granulosa cells with phorbol 12-myristate 13-acetate (PMA) enhanced LH- and forskolin-stimulated cAMP levels. SRIF-14 failed to inhibit LH- or forskolin-stimulated cAMP levels in cells preincubated with PMA. It is concluded that SRIF-14 inhibits hormone-stimulated cAMP induction in the porcine ovary. LH-induced protein kinase C activation may be physiologically important to alleviate the inhibitory effects of SRIF-14. Journal of Endocrinology (1992) 134, 297–306

scholarly journals Iodide symporter gene expression in normal and transformed rat thyroid cells

1999 ◽  
pp. 447-451 ◽  
Author(s):  
F Trapasso ◽  
R Iuliano ◽  
E Chiefari ◽  
F Arturi ◽  
A Stella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Transformed Cell ◽  
Nis Gene ◽  
Rat Thyroid ◽  
Transformed Cell Lines

OBJECTIVE: Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells. DESIGN AND METHODS: Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability. RESULTS: NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA, PC HaMSV, PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala), and PC PyMLV cell lines. CONCLUSIONS: Our data show that oncogene activation could play a role in affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.

Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells

2008 ◽  
Vol 294 (4) ◽  
pp. E802-E806 ◽  
Author(s):  
Neil Tran ◽  
Liza Valentín-Blasini ◽  
Benjamin C. Blount ◽  
Caroline Gibbs McCuistion ◽  
Mike S. Fenton ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Active Transport ◽  
Measurement Techniques ◽  
Thyroid Stimulating Hormone ◽  
Dependent Manner ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Inhibit Cell Proliferation ◽  
Stimulating Hormone

Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1–10 μM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 μM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 μM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation.

Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells

1995 ◽  
Vol 132 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Mariko Arai ◽  
Toshio Tsushima ◽  
Osamu Isozaki ◽  
Hiroshi Demura ◽  
Kazuo Shizume ◽  
...  
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Dependent Manner ◽  
Camp Production ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Transforming Growth Factor Α ◽  
Iodine Metabolism ◽  
Factor Α

Arai M, Tsushima T, Isozaki 0, Demura H, Shizume K, Emoto N, Miyakawa M, Nozoe Y, Murakami H, Ohmura E. Effects of transforming growth factor α (TGF-α) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells. Eur J Endocrinol 1995;132:242–8. ISSN 0804–4643 Transforming growth factor α (TGF-α) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-α has similar effects using porcine thyroid cells in culture. Recombinant human TGF-α dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-α is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-α, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-α again was approximately 50% that of EGF. Transforming growth factor α did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-α. Thus, we conclude that TGF-α inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-α mRNA in porcine thyroid cells. These observations suggest that TGF-α acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells. T Tsushima, Department of Medicine 2, Tokyo Women's Medical College, Kawadacho 8–1, Shinjukuku, Tokyo 162, Japan

scholarly journals Brassinolide Enhances the Level of Brassinosteroids, Protein, Pigments, and Monosaccharides in Wolffia arrhiza Treated with Brassinazole

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1311
Author(s):  
Magdalena Chmur ◽  
Andrzej Bajguz
Keyword(s):  
Plant Growth ◽  
Growth And Development ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Plant Growth And Development ◽  
Concentration Dependent Manner ◽  
Spectrophotometric Methods ◽  
Synthetic Inhibitor ◽  
Wolffia Arrhiza ◽  
First Time

Brassinolide (BL) represents brassinosteroids (BRs)—a group of phytohormones that are essential for plant growth and development. Brassinazole (Brz) is as a synthetic inhibitor of BRs’ biosynthesis. In the present study, the responses of Wolffia arrhiza to the treatment with BL, Brz, and the combination of BL with Brz were analyzed. The analysis of BRs and Brz was performed using LC-MS/MS. The photosynthetic pigments (chlorophylls, carotenes, and xanthophylls) levels were determined using HPLC, but protein and monosaccharides level using spectrophotometric methods. The obtained results indicated that BL and Brz influence W. arrhiza cultures in a concentration-dependent manner. The most stimulatory effects on the growth, level of BRs (BL, 24-epibrassinolide, 28-homobrassinolide, 28-norbrassinolide, catasterone, castasterone, 24-epicastasterone, typhasterol, and 6-deoxytyphasterol), and the content of pigments, protein, and monosaccharides, were observed in plants treated with 0.1 µM BL. Whereas the application of 1 µM and 10 µM Brz caused a significant decrease in duckweed weight and level of targeted compounds. Application of BL caused the mitigation of the Brz inhibitory effect and enhanced the BR level in duckweed treated with Brz. The level of BRs was reported for the first time in duckweed treated with BL and/or Brz.

scholarly journals Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

Fibrinogen binding to the integrin αIIbβ3 modulates store-mediated calcium entry in human platelets

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2648-2656 ◽  
Author(s):  
Juan A. Rosado ◽  
Else M. Y. Meijer ◽  
Karly Hamulyak ◽  
Irena Novakova ◽  
Johan W. M. Heemskerk ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Actin Polymerization ◽  
Adenosine Diphosphate ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Integrin Αiibβ3 ◽  
Fibrinogen Binding

Abstract Effects of the occupation of integrin αIIbβ3 by fibrinogen on Ca++signaling in fura-2–loaded human platelets were investigated. Adding fibrinogen to washed platelet suspensions inhibited increases in cytosolic [Ca++] concentrations ([Ca++]i) evoked by adenosine diphosphate (ADP) and thrombin in a concentration-dependent manner in the presence of external Ca++ but not in the absence of external Ca++ or in the presence of the nonselective cation channel blocker SKF96365, indicating selective inhibition of Ca++entry. Fibrinogen also inhibited store-mediated Ca++ entry (SMCE) activated after Ca++ store depletion using thapsigargin. The inhibitory effect of fibrinogen was reversed if fibrinogen binding to αIIbβ3 was blocked using RDGS or abciximab and was absent in platelets from patients homozygous for Glanzmann thrombasthenia. Fibrinogen was without effect on SMCE once activated. Activation of SMCE in platelets occurs through conformational coupling between the intracellular stores and the plasma membrane and requires remodeling of the actin cytoskeleton. Fibrinogen inhibited actin polymerization evoked by ADP or thapsigargin in control cells and in cells loaded with the Ca++ chelator dimethyl BAPTA. It also inhibited the translocation of the tyrosine kinase p60src to the cytoskeleton. These results indicate that the binding of fibrinogen to integrin αIIbβ3 inhibits the activation of SMCE in platelets by a mechanism that may involve modulation of the reorganization of the actin cytoskeleton and the cytoskeletal association of p60src. This action may be important in intrinsic negative feedback to prevent the further activation of platelets subjected to low-level stimuli in vivo.

Thrombin activatable fibrinolysis inhibitor (TAFI) affects fibrinolysis in a plasminogen activator concentration-dependent manner

2004 ◽  
Vol 91 (03) ◽  
pp. 473-479 ◽  
Author(s):  
Ana Guimarães ◽  
Dingeman Rijken
Keyword(s):  
Plasminogen Activator ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Retardation Factor ◽  
Clot Lysis ◽  
Dependent Manner ◽  
Plasma Clot ◽  
Concentration Dependent Manner ◽  
Plasmin Inhibitor

SummaryTAFIa was shown to attenuate fibrinolysis. In our in vitro study, we investigated how the inhibitory effect of TAFIa depended on the type and concentration of the plasminogen activator (PA). We measured PA-mediated lysis times of plasma clots under conditions of maximal TAFI activation by thrombin-thrombomodulin in the absence and presence of potato carboxypeptidase inhibitor. Seven different PAs were compared comprising both tPA-related (tPA, TNK-tPA, DSPA), bacterial PA-related (staphylokinase and APSAC) and urokinase-related (tcu-PA and k2tu-PA) PAs. The lysis times and the retardation factor were plotted against the PA concentration. The retardation factor plots were bell-shaped. At low PA concentrations, the retardation factor was low, probably due to the limited stability of TAFIa. At intermediate PA concentrations the retardation factor was maximal (3-6 depending on the PA), with TNK-tPA, APSAC and DSPA exhibiting the strongest effect. At high PA concentrations, the retardation factor was again low, possibly due to inactivation of TAFIa by plasmin or to a complete conversion of glu-plasminogen into lys-plasminogen. Using individual plasmas with a reduced plasmin inhibitor activity (plasmin inhibitor Enschede) the bell-shaped curve of the retardation factor shifted towards lower tPA and DSPA concentrations, but the height did not decrease. In conclusion, TAFIa delays the lysis of plasma clots mediated by all the plasminogen activators tested. This delay is dependent on the type and concentration of the plasminogen activator, but not on the fibrin specificity of the plasminogen activator. Furthermore, plasmin inhibitor does not play a significant role in the inhibition of plasma clot lysis by TAFI.

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