On the mechanism of the reduction by thyroid hormone of beta-adrenergic relaxation rate stimulation in rat heart.
The effects of beta-adrenergic stimulation on the relaxation rate and the Ca2+-transport rate in sarcoplasmic reticulum of hypothyroid, euthyroid and hyperthyroid rat hearts were studied. Administration of isoproterenol (0.1 microM) to perfused, electrically stimulated hearts (5 Hz) caused a decrease in the half-time of relaxation (RT 1/2) the extent of which depended on the thyroid status, i.e. hypothyroid (-24%), euthyroid (-19%) or hyperthyroid (-8%). A similar decreasing effect was found for the stimulation of Ca2+ transport in isolated SR by cyclic AMP and protein kinase, i.e. hypothyroid (75%), euthyroid (37%) and hyperthyroid (20%). These alterations were not due to differences in endogenous protein kinase activity or cyclic AMP production. Estimations of Ca2+-ATPase and phospholamban (PL) content of the sarcoplasmic reticulum were obtained by measurement of the phosphorylated forms of Ca2+-ATPase (E-P) and phospholamban (PL-P) followed by electrophoresis and autoradiography. A 3-fold decrease of PL-P, accompanied by a 2-fold increase of E-P per mg of protein was observed in sarcoplasmic reticulum preparations in the direction hypothyroid----hyperthyroid. Consequently the E-P/PL-P ratio increased from 0.32 (hypothyroid), through 0.81 (euthyroid) to 1.69 (hyperthyroid). In spite of certain limitations inherent to quantification of Ca2+-ATPase and phospholamban by their phosphorylated products, these data provide strong evidence that during thyroid-hormone mediated cardiac hypertrophy, with concomitant proliferation of the sarcoplasmic reticulum, the relative amount of phospholamban decreases with respect to Ca2+-ATPase. This could provide an explanation for the observed gradual diminishment of the beta-adrenergic effect on the relaxation rate when cardiac tissue is exposed to increasing amounts of thyroid hormone.
Beekman
R E
RE
Laboratory for Physiology, Free University, Amsterdam, The Netherlands.
van Hardeveld
C
C
Simonides
W S
WS
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013963:Thyroid Hormones / Q000502:physiology*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000242:Cyclic AMP; D007545:Isoproterenol; D013963:Thyroid Hormones; D000099211:Phospholamban