Kinetics of Thyroxine (T4) and Triiodothyronine (T3) Transport in the Isolated Rat Heart

The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125I‐thyroxine (125I‐T4) and 125I‐triiodothyronine (125I‐T3) from the extracellular space into heart cells was measured relative to the extracellular space marker 3H‐mannitol. The thyroid hormone maximal uptake was 54.4% for 125I‐T4 and 52.15% for 125I‐T3. The thyroid hormone net uptake was 25.69% for 125I‐T4 and 25.49% for 125I‐T3. Backflux from the intracellular space was 53.17% for 125I‐T4 and 61.59% for 125I‐T3. In the presence of unlabelled thyroid hormones, 125I‐T4 and 125I‐T3 maximal uptakes were reduced from 10.1 to 59.74% and from 34.6 to 65.3%, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with Km(T4)= 105.46 μM and the maximal rate of 125I‐thyroid hormone flux from the extracellular space to heart cells (Vmax(T4)) = 177.84 nM min−1 for 125I‐T4 uptake, and Km(T3)= 80.0 μM and Vmax(T3)= 118.5 nM min−1 for 125I‐T3 uptake.

[1]  G. Mann,et al.  Unidirectional uptake of substrates at the blood side of secretory epithelia: stomach, salivary gland, pancreas. , 1982, Federation proceedings.

[2]  J. Preston,et al.  The uptake of anionic and cationic amino acids by the isolated perfused sheep choroid plexus , 1992, Brain Research.

[3]  J. Moolman.  Thyroid hormone and the heart. , 2002, Cardiovascular journal of South Africa : official journal for Southern Africa Cardiac Society [and] South African Society of Cardiac Practitioners.

[4]  J. Preston,et al.  Saturable uptake of [125I]l-triiodothyronine at the basolateral (blood) and apical (cerebrospinal fluid) sides of the isolated perfused sheep choroid plexus , 1992, Brain Research.

[5]  J. Franklyn,et al.  Thyroid disease: Effects on cardiovascular function , 1996, Trends in Endocrinology & Metabolism.

[6]  G. Mann,et al.  Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart. , 1984, The Journal of physiology.

[7]  Moore,et al.  Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected beta type thyroid hormone receptor. , 1989, The Journal of biological chemistry.

[8]  O. Nallet,et al.  Alpha-, beta-MHC mRNA quantification in adult cardiomyocytes by in situhybridization: effect of thyroid hormone. , 1993, The American journal of physiology.

[9]  P. Larsen,et al.  Thyroid hormone regulation of gene expression. , 1991, Annual review of physiology.

[10]  H. Samuels,et al.  Regulation of gene expression by thyroid hormone. , 1988, The Journal of clinical investigation.

[11]  E. Webb,et al.  Non-Inverted Versus Inverted Plots in Enzyme Kinetics , 1959, Nature.

[12]  I. Klein,et al.  In vivo regulation of recombinant cardiac myosin heavy chain gene expression by thyroid hormone. , 1993, Endocrinology.

[13]  F. Huang,et al.  Thyroid hormone regulation of Na,K-ATPase alpha 2 gene expression in cardiac myocytes. , 1994, Cellular & molecular biology research.

[14]  N. Wong,et al.  Advances in our understanding of thyroid hormone action at the cellular level. , 1987, Endocrine reviews.

[15]  T. Nagaya,et al.  Heterodimerization preferences of thyroid hormone receptor alpha isoforms. , 1996, Biochemical and Biophysical Research Communications - BBRC.

[16]  K. Otsu,et al.  Thyroid hormone enhances Ca2+ pumping activity of the cardiac sarcoplasmic reticulum by increasing Ca2+ ATPase and decreasing phospholamban expression. , 1994, Journal of molecular and cellular cardiology.

[17]  M. Rosic,et al.  Biphasic L-arginine uptake by the isolated guinea-pig heart. , 1992, Experimental physiology.

[18]  F. Greenwood,et al.  Preparation of Iodine-131 Labelled Human Growth Hormone of High Specific Activity , 1962, Nature.

[19]  T. Slotkin,et al.  Thyroid hormone regulates ontogeny of beta adrenergic receptors and adenylate cyclase in rat heart and kidney: effects of propylthiouracil-induced perinatal hypothyroidism. , 1992, The Journal of pharmacology and experimental therapeutics.