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Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes

Departments of 1  Internal Medicine III and 2  Biochemistry, Erasmus University Medical School, 3000 DR Rotterdam; and 3  Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands The effects of the Ca 2+ channel blockers verapamil, nifedipine, and diltiaz...

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Published in:American journal of physiology. Heart and circulatory physiology 2001-11, Vol.281 (5), p.H1985-H1991
Main Authors: Verhoeven, Frank A, Moerings, Ellis P. C. M, Lamers, Jos M. J, Hennemann, Georg, Visser, Theo J, Everts, Maria E
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container_end_page H1991
container_issue 5
container_start_page H1985
container_title American journal of physiology. Heart and circulatory physiology
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creator Verhoeven, Frank A
Moerings, Ellis P. C. M
Lamers, Jos M. J
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Visser, Theo J
Everts, Maria E
description Departments of 1  Internal Medicine III and 2  Biochemistry, Erasmus University Medical School, 3000 DR Rotterdam; and 3  Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands The effects of the Ca 2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T 3 ) and thyroxine (T 4 ) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37°C in medium with 0.5% BSA for [ 125 I]T 3 (100 pM) or 0.1% BSA for [ 125 I]T 4 (350 pM). The 15-min uptake of [ 125 I]T 3 was 0.124 ± 0.013 fmol/pM free T 3 ( n  = 6); [ 125 I]T 4 uptake was 0.032 ± 0.003 fmol/pM free T 4 ( n  = 12). Neither T 3 nor T 4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [ 125 I]T 3 but not of [ 125 I]T 4 was dose dependently reduced by incubation with 1-100 µM verapamil (49-87%, P  
doi_str_mv 10.1152/ajpheart.2001.281.5.H1985
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C. M ; Lamers, Jos M. J ; Hennemann, Georg ; Visser, Theo J ; Everts, Maria E</creator><creatorcontrib>Verhoeven, Frank A ; Moerings, Ellis P. C. M ; Lamers, Jos M. J ; Hennemann, Georg ; Visser, Theo J ; Everts, Maria E</creatorcontrib><description>Departments of 1  Internal Medicine III and 2  Biochemistry, Erasmus University Medical School, 3000 DR Rotterdam; and 3  Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands The effects of the Ca 2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T 3 ) and thyroxine (T 4 ) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37°C in medium with 0.5% BSA for [ 125 I]T 3 (100 pM) or 0.1% BSA for [ 125 I]T 4 (350 pM). The 15-min uptake of [ 125 I]T 3 was 0.124 ± 0.013 fmol/pM free T 3 ( n  = 6); [ 125 I]T 4 uptake was 0.032 ± 0.003 fmol/pM free T 4 ( n  = 12). Neither T 3 nor T 4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [ 125 I]T 3 but not of [ 125 I]T 4 was dose dependently reduced by incubation with 1-100 µM verapamil (49-87%, P  &lt; 0.05) or nifedipine (53-81%, P  &lt; 0.05). The relative decline in [ 125 I]T 3 uptake after 4 h of incubation with 10 µM verapamil or nifedipine was less than after 15 min or 1 h, indicating that the major inhibitory effect of the Ca 2+ channel blockers occurred at the level of the plasma membrane. The reduction of nuclear [ 125 I]T 3 binding by 10 µM verapamil or nifedipine was proportional to the reduction of cellular [ 125 I]T 3 uptake. Diltiazem (1-100 µM) had no dose-dependent effect on [ 125 I]T 3 uptake but reduced [ 125 I]T 4 uptake by 45% ( P  &lt; 0.05) at each concentration tested. Neither the presence of 20 mM K + nor the presence of low Ca 2+ in the medium affected [ 125 I]T 3 uptake. 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J</creatorcontrib><creatorcontrib>Hennemann, Georg</creatorcontrib><creatorcontrib>Visser, Theo J</creatorcontrib><creatorcontrib>Everts, Maria E</creatorcontrib><title>Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol Heart Circ Physiol</addtitle><description>Departments of 1  Internal Medicine III and 2  Biochemistry, Erasmus University Medical School, 3000 DR Rotterdam; and 3  Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands The effects of the Ca 2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T 3 ) and thyroxine (T 4 ) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37°C in medium with 0.5% BSA for [ 125 I]T 3 (100 pM) or 0.1% BSA for [ 125 I]T 4 (350 pM). The 15-min uptake of [ 125 I]T 3 was 0.124 ± 0.013 fmol/pM free T 3 ( n  = 6); [ 125 I]T 4 uptake was 0.032 ± 0.003 fmol/pM free T 4 ( n  = 12). Neither T 3 nor T 4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [ 125 I]T 3 but not of [ 125 I]T 4 was dose dependently reduced by incubation with 1-100 µM verapamil (49-87%, P  &lt; 0.05) or nifedipine (53-81%, P  &lt; 0.05). The relative decline in [ 125 I]T 3 uptake after 4 h of incubation with 10 µM verapamil or nifedipine was less than after 15 min or 1 h, indicating that the major inhibitory effect of the Ca 2+ channel blockers occurred at the level of the plasma membrane. The reduction of nuclear [ 125 I]T 3 binding by 10 µM verapamil or nifedipine was proportional to the reduction of cellular [ 125 I]T 3 uptake. Diltiazem (1-100 µM) had no dose-dependent effect on [ 125 I]T 3 uptake but reduced [ 125 I]T 4 uptake by 45% ( P  &lt; 0.05) at each concentration tested. Neither the presence of 20 mM K + nor the presence of low Ca 2+ in the medium affected [ 125 I]T 3 uptake. 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Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>281</volume><issue>5</issue><spage>H1985</spage><epage>H1991</epage><pages>H1985-H1991</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><abstract>Departments of 1  Internal Medicine III and 2  Biochemistry, Erasmus University Medical School, 3000 DR Rotterdam; and 3  Department of Veterinary Anatomy and Physiology, Utrecht University, 3508 TD Utrecht, The Netherlands The effects of the Ca 2+ channel blockers verapamil, nifedipine, and diltiazem on triiodothyronine (T 3 ) and thyroxine (T 4 ) uptake were tested in cultured cardiomyocytes from 2-day-old rats. Experiments were performed at 37°C in medium with 0.5% BSA for [ 125 I]T 3 (100 pM) or 0.1% BSA for [ 125 I]T 4 (350 pM). The 15-min uptake of [ 125 I]T 3 was 0.124 ± 0.013 fmol/pM free T 3 ( n  = 6); [ 125 I]T 4 uptake was 0.032 ± 0.003 fmol/pM free T 4 ( n  = 12). Neither T 3 nor T 4 uptake was affected by 1% DMSO (diluent for nifedipine and verapamil). Uptake of [ 125 I]T 3 but not of [ 125 I]T 4 was dose dependently reduced by incubation with 1-100 µM verapamil (49-87%, P  &lt; 0.05) or nifedipine (53-81%, P  &lt; 0.05). The relative decline in [ 125 I]T 3 uptake after 4 h of incubation with 10 µM verapamil or nifedipine was less than after 15 min or 1 h, indicating that the major inhibitory effect of the Ca 2+ channel blockers occurred at the level of the plasma membrane. The reduction of nuclear [ 125 I]T 3 binding by 10 µM verapamil or nifedipine was proportional to the reduction of cellular [ 125 I]T 3 uptake. Diltiazem (1-100 µM) had no dose-dependent effect on [ 125 I]T 3 uptake but reduced [ 125 I]T 4 uptake by 45% ( P  &lt; 0.05) at each concentration tested. Neither the presence of 20 mM K + nor the presence of low Ca 2+ in the medium affected [ 125 I]T 3 uptake. In conclusion, the inhibitory effects of Ca 2+ channel blockers on T 3 uptake in cardiomyocytes are not secondary to their effects on Ca 2+ influx but, rather, reflect interference with the putative T 3 carrier in the plasma membrane. heart; culture; ATP; free hormone fraction</abstract><cop>United States</cop><pmid>11668059</pmid><doi>10.1152/ajpheart.2001.281.5.H1985</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0363-6135
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subjects Adenosine Triphosphate - metabolism
Animals
Animals, Newborn
Biological Transport - drug effects
Calcium - pharmacology
Calcium Channel Blockers - pharmacology
Cell Membrane - metabolism
Cells, Cultured
Diltiazem - pharmacology
Iodine Radioisotopes
Muscle Fibers, Skeletal - cytology
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - metabolism
Myocardium - cytology
Nifedipine - pharmacology
Potassium - pharmacology
Rats
Rats, Wistar
Thyroxine - pharmacokinetics
Triiodothyronine - pharmacokinetics
Verapamil - pharmacology
title Inhibitory effects of calcium channel blockers on thyroid hormone uptake in neonatal rat cardiomyocytes
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