Thyroxine and propylthiouracil effects on alpha- and beta-adrenergic receptor number, ATPase activities, and sialic acid content of rat cardiac membrane vesicles

Mona M. McConnaughey, Larry R. Jones, August M. Watanabe, Henry R. Besch, Lewis T. Williams, Robert J. Lefkowitz

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Membrane vesicle preparations from the hearts of euthyroid, hyperthyroid, and hypothyroid rats were analyzed in an attempt to identify biochemical changes which might correlate with known functional changes occurring in these thyroid states. Several sarcolemmal constituents which have been shown to influence myocardial contractility were measured in membrane vesicle preparations from the hearts of animals in the three thyroid states. These constituents included the apparent number of alpha- and beta-adrenergic receptors (judged from specific binding of radiolabeled adrenergic antagonists) and Na<sup>-</sup>, K<sup>-</sup>-ATPase activity. As a control for the recovery of sarcolemma in the preparations, the sialic acid content was measured in all preparations. The activity of K<sup>-</sup>, Ca<sup>2-</sup>-ATPase, a sarcoplasmic reticulum enzyme which regulates intracellular ionized Ca<sup>2-</sup> concentration, was also measured. Membrane vesicles of the thyroxine-treated hyperthyroid rats showed a decrease (41%, p < 0.01) in the total apparent number of alpha-adrenergic receptors relative to euthyroid controls and an increase in the total apparent number of beta-adrenergic receptors (43%, p < 0.001). Membrane vesicles prepared from propylthiouracil-treated hypothyroid rats showed a decrease relative to euthyroid controls in the total apparent number of both alpha-adrenergic receptors (29%, p < 0.01) and beta-adrenergic receptors (23%, p < 0.05). The ratio of beta- to alpha-receptors approximately doubled in the hyperthyroid animals but remained unchanged compared to controls in the membranes isolated from hypothyroid animals. In the same membrane vesicle preparations, total sialic acid content was similar regardless of thyroid state. In addition. both Na<sup>+</sup>,K<sup>+</sup>-ATPase and K<sup>-</sup>,Ca<sup>2-</sup>-ATPase activities remained unchanged when activities measured in membranes from euthyroid rats were compared to activities obtained from hyperthyroid rats. In membrane preparations isolated from hypothyroid rats, however, Na<sup>+</sup>,K<sup>+</sup>-ATPase and K<sup>-</sup>,Ca<sup>2-</sup>-ATPase activities were decreased approximately 40% (p < 0.005). The results suggest that with hyperthyroidism the increased sensitivity of myocardium to catecholamines may reflect an alteration in the apparent number of alpha- and beta-adrenergic receptors in the sarcolemma. These changes occur while the Na<sup>+</sup>,K<sup>+</sup>-ATPase activity of sarcolemma and the K<sup>+</sup>,Ca<sup>2+</sup>-ATPase activity of sarcoplasmic reticulum remain constant. The same biochemical parameters are more diffusely altered with hypothyroidism, however, and changes occur both at the level of the sarcolemma and the sarcoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)609-623
Number of pages15
JournalJournal of cardiovascular pharmacology
Volume1
Issue number6
StatePublished - Jan 1 1979

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Propylthiouracil
Receptors, Adrenergic, alpha
Receptors, Adrenergic, beta
N-Acetylneuraminic Acid
Thyroxine
Calcium-Transporting ATPases
Adenosine Triphosphatases
Sarcolemma
Sarcoplasmic Reticulum
Hyperthyroidism
Membranes
Thyroid Gland
Adrenergic Antagonists
Hypothyroidism
Enzymes

Keywords

  • Adrenergic receptors
  • Sarcolemma
  • Sarcoplasmic reticulum
  • Thyroid hormone regulation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Thyroxine and propylthiouracil effects on alpha- and beta-adrenergic receptor number, ATPase activities, and sialic acid content of rat cardiac membrane vesicles. / McConnaughey, Mona M.; Jones, Larry R.; Watanabe, August M.; Besch, Henry R.; Williams, Lewis T.; Lefkowitz, Robert J.

In: Journal of cardiovascular pharmacology, Vol. 1, No. 6, 01.01.1979, p. 609-623.

Research output: Contribution to journalArticle

McConnaughey, Mona M. ; Jones, Larry R. ; Watanabe, August M. ; Besch, Henry R. ; Williams, Lewis T. ; Lefkowitz, Robert J. / Thyroxine and propylthiouracil effects on alpha- and beta-adrenergic receptor number, ATPase activities, and sialic acid content of rat cardiac membrane vesicles. In: Journal of cardiovascular pharmacology. 1979 ; Vol. 1, No. 6. pp. 609-623.
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abstract = "Membrane vesicle preparations from the hearts of euthyroid, hyperthyroid, and hypothyroid rats were analyzed in an attempt to identify biochemical changes which might correlate with known functional changes occurring in these thyroid states. Several sarcolemmal constituents which have been shown to influence myocardial contractility were measured in membrane vesicle preparations from the hearts of animals in the three thyroid states. These constituents included the apparent number of alpha- and beta-adrenergic receptors (judged from specific binding of radiolabeled adrenergic antagonists) and Na-, K--ATPase activity. As a control for the recovery of sarcolemma in the preparations, the sialic acid content was measured in all preparations. The activity of K-, Ca2--ATPase, a sarcoplasmic reticulum enzyme which regulates intracellular ionized Ca2- concentration, was also measured. Membrane vesicles of the thyroxine-treated hyperthyroid rats showed a decrease (41{\%}, p < 0.01) in the total apparent number of alpha-adrenergic receptors relative to euthyroid controls and an increase in the total apparent number of beta-adrenergic receptors (43{\%}, p < 0.001). Membrane vesicles prepared from propylthiouracil-treated hypothyroid rats showed a decrease relative to euthyroid controls in the total apparent number of both alpha-adrenergic receptors (29{\%}, p < 0.01) and beta-adrenergic receptors (23{\%}, p < 0.05). The ratio of beta- to alpha-receptors approximately doubled in the hyperthyroid animals but remained unchanged compared to controls in the membranes isolated from hypothyroid animals. In the same membrane vesicle preparations, total sialic acid content was similar regardless of thyroid state. In addition. both Na+,K+-ATPase and K-,Ca2--ATPase activities remained unchanged when activities measured in membranes from euthyroid rats were compared to activities obtained from hyperthyroid rats. In membrane preparations isolated from hypothyroid rats, however, Na+,K+-ATPase and K-,Ca2--ATPase activities were decreased approximately 40{\%} (p < 0.005). The results suggest that with hyperthyroidism the increased sensitivity of myocardium to catecholamines may reflect an alteration in the apparent number of alpha- and beta-adrenergic receptors in the sarcolemma. These changes occur while the Na+,K+-ATPase activity of sarcolemma and the K+,Ca2+-ATPase activity of sarcoplasmic reticulum remain constant. The same biochemical parameters are more diffusely altered with hypothyroidism, however, and changes occur both at the level of the sarcolemma and the sarcoplasmic reticulum.",
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AU - Jones, Larry R.

AU - Watanabe, August M.

AU - Besch, Henry R.

AU - Williams, Lewis T.

AU - Lefkowitz, Robert J.

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N2 - Membrane vesicle preparations from the hearts of euthyroid, hyperthyroid, and hypothyroid rats were analyzed in an attempt to identify biochemical changes which might correlate with known functional changes occurring in these thyroid states. Several sarcolemmal constituents which have been shown to influence myocardial contractility were measured in membrane vesicle preparations from the hearts of animals in the three thyroid states. These constituents included the apparent number of alpha- and beta-adrenergic receptors (judged from specific binding of radiolabeled adrenergic antagonists) and Na-, K--ATPase activity. As a control for the recovery of sarcolemma in the preparations, the sialic acid content was measured in all preparations. The activity of K-, Ca2--ATPase, a sarcoplasmic reticulum enzyme which regulates intracellular ionized Ca2- concentration, was also measured. Membrane vesicles of the thyroxine-treated hyperthyroid rats showed a decrease (41%, p < 0.01) in the total apparent number of alpha-adrenergic receptors relative to euthyroid controls and an increase in the total apparent number of beta-adrenergic receptors (43%, p < 0.001). Membrane vesicles prepared from propylthiouracil-treated hypothyroid rats showed a decrease relative to euthyroid controls in the total apparent number of both alpha-adrenergic receptors (29%, p < 0.01) and beta-adrenergic receptors (23%, p < 0.05). The ratio of beta- to alpha-receptors approximately doubled in the hyperthyroid animals but remained unchanged compared to controls in the membranes isolated from hypothyroid animals. In the same membrane vesicle preparations, total sialic acid content was similar regardless of thyroid state. In addition. both Na+,K+-ATPase and K-,Ca2--ATPase activities remained unchanged when activities measured in membranes from euthyroid rats were compared to activities obtained from hyperthyroid rats. In membrane preparations isolated from hypothyroid rats, however, Na+,K+-ATPase and K-,Ca2--ATPase activities were decreased approximately 40% (p < 0.005). The results suggest that with hyperthyroidism the increased sensitivity of myocardium to catecholamines may reflect an alteration in the apparent number of alpha- and beta-adrenergic receptors in the sarcolemma. These changes occur while the Na+,K+-ATPase activity of sarcolemma and the K+,Ca2+-ATPase activity of sarcoplasmic reticulum remain constant. The same biochemical parameters are more diffusely altered with hypothyroidism, however, and changes occur both at the level of the sarcolemma and the sarcoplasmic reticulum.

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KW - Adrenergic receptors

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