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

Journal Article · Thu Dec 01 04:00:00 EST 1988 · American Journal of Physiology; (USA)

OSTI ID:6038762

Haber, R S; Loeb, J N ^[1]

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1. Columbia Univ., New York, NY (USA)

The administration of thyroid hormone is known to result in an induction of the Na{sup +}-K{sup +}-adenosinetriphosphatase (Na{sup +}-K{sup +}-ATPase) in rat skeletal muscle and other thyroid hormone-responsive tissues. Since the Na{sup +}-K{sup +}-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. The authors have studied the effects of 3,3{prime},5-triiodo-L-thyronine (T{sub 3}) treatment on these two forms of the enzyme in rat diaphragm. The inhibition of Na{sup +}-K{sup +}-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 (K{sub I}s) for ouabain of {approximately}10{sup {minus}7} and 10{sup {minus}4} M, respectively. Measurement of the specific binding of ({sup 3}H)ouabain to these membranes confirmed the presence of a class of high-affinity ouabain binding sites with a dissociation constant (K{sub d}) of slightly less than 10{sup {minus}7}M, whose maximal binding capacity was increased by T{sub 3} treatment by 185%. Binding studies in unfractionated homogenates of diaphragm similarly demonstrated the presence of high-affinity sites whose maximal binding capacity was increased by T{sub 3} treatment. Quantitation of both the high- and low-ouabain-affinity forms of the Na{sup +}-K{sup +}-ATPase by ouabain-dependent phosphorylation from ({sup 32}P)orthophosphate confirmed that T{sub 3} treatment markedly increased the number of high-affinity sites while having little effect on the number of low-affinity sites. These observations provide, to our knowledge, the first demonstration that these two forms of the Na{sup +}-K{sup +}-ATPase are subject to selective hormonal induction.

• OSTI ID: 6038762
• Journal Information: American Journal of Physiology; (USA), Journal Name: American Journal of Physiology; (USA) Vol. 255:6; ISSN 0002-9513; ISSN AJPHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
AMINO ACIDS
ANIMALS
ATP-ASE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIAC GLYCOSIDES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHEMICAL REACTIONS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ENDOCRINE DISEASES
ENZYME INDUCTION
ENZYMES
GENE REGULATION
GLYCOSIDES
HORMONES
HYDROGEN COMPOUNDS
HYDROLASES
HYDROXY ACIDS
HYPOTHYROIDISM
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MUSCLES
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
OUABAIN
PEPTIDE HORMONES
PHOSPHOHYDROLASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORYLATION
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
STROPHANTHINS
THYRONINE
TRITIUM COMPOUNDS
VERTEBRATES