Selective induction of high-ouabain-affinity isoform of Na+-K+-ATPase by thyroid hormone. 1988

R S Haber, and J N Loeb
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032.

The administration of thyroid hormone is known to result in an induction of the Na+-K+-adenosinetriphosphatase (Na+-K+-ATPase) in rat skeletal muscle and other thyroid hormone-responsive tissues. Since the Na+-K+-ATPase in a variety of mammalian tissues has recently been reported to exist in at least two forms distinguishable by differing affinities for the inhibitory cardiac glycoside ouabain, we have studied the effects of 3,3',5-triiodo-L-thyronine (T3) treatment on these two forms of the enzyme in rat diaphragm. The inhibition of Na+-K+-ATPase activity in a crude membrane fraction by varying concentrations of ouabain conformed to a biphasic pattern consistent with the presence of two distinct isoforms with inhibition constants (KIs) for ouabain of approximately 10(-7) and 10(-4) M, respectively. Treatment of hypothyroid rats with T3 (50 micrograms/100 g body wt on 3 alternate days) nearly tripled that portion of the Na+-K+-ATPase activity corresponding to the high-ouabain-affinity form (increased by 178 +/- 24%), whereas the enzyme activity corresponding to the low-ouabain-affinity form was only slightly changed (increased by 20 +/- 5%). Measurement of the specific binding of [3H]ouabain to these membranes confirmed the presence of a class of high-affinity ouabain binding sites with a dissociation constant (Kd) of slightly less than 10(-7) M, whose maximal binding capacity was increased by T3 treatment by 185%. The calculated catalytic turnover associated with the high-affinity site was 70-80 molecules ATP hydrolyzed.site-1.s-1 and was unchanged by T3 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D007037 Hypothyroidism A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction. Central Hypothyroidism,Primary Hypothyroidism,Secondary Hypothyroidism,TSH Deficiency,Thyroid-Stimulating Hormone Deficiency,Central Hypothyroidisms,Deficiency, TSH,Deficiency, Thyroid-Stimulating Hormone,Hormone Deficiency, Thyroid-Stimulating,Hypothyroidism, Central,Hypothyroidism, Primary,Hypothyroidism, Secondary,Hypothyroidisms,Primary Hypothyroidisms,Secondary Hypothyroidisms,TSH Deficiencies,Thyroid Stimulating Hormone Deficiency,Thyroid-Stimulating Hormone Deficiencies
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D009132 Muscles Contractile tissue that produces movement in animals. Muscle Tissue,Muscle,Muscle Tissues,Tissue, Muscle,Tissues, Muscle
D010042 Ouabain A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE. Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012016 Reference Values The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003964 Diaphragm The musculofibrous partition that separates the THORACIC CAVITY from the ABDOMINAL CAVITY. Contraction of the diaphragm increases the volume of the thoracic cavity aiding INHALATION. Respiratory Diaphragm,Diaphragm, Respiratory,Diaphragms,Diaphragms, Respiratory,Respiratory Diaphragms

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