Article: PDF OnlyThyroid Hormone Regulation of Alpha-Adrenergic Receptors Studies in Rat MyocardiumWilliams, R. Sanders*; Lefkowitz, Robert J.*†Author Information *Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27710 †Department of Biochemistry, Duke University School of Medicine, Durham, North Carolina 27710 Journal of Cardiovascular Pharmacology: March 1979 - Volume 1 - Issue 2 - p 181-190 Free Abstract Summary The effects of alterations in thyroid state on cardiac alpha-adrenergic receptors were investigated by the binding of [3H]dihydroergocryptine (DHE), a potent alpha-adrenergic antagonist. In seven experiments, cardiac membranes from euthyroid rats bound 47 ± 9 fmoles DHE/mg protein (mean ± SE) at saturation and demonstrated a dissociation constant (KD) of 2.5 ± 0.4 nM. Hyperthyroidism, produced by parenteral injection of triiodothyronine, significantly reduced the binding of DHE at all concentrations studied. Scatchard analysis showed this reduction of binding to be due largely to a decreased affinity (KD = 4.0 ± 0.8 nM, p < 0.05), although possibly due to a decreased number of binding sites as well (29 ± 7 fmoles/mg protein, p < 0.10). Hypothyroidism, produced either by oral propylthiouracil or by surgical thyroidectomy, did not produce a significant change in either the number of binding sites for DHE (56 ± 8 fmoles/mg protein, p < 0.40) or in binding affinity (KD = 3.1 ± 0.5 nM, p < 0.40). Thus, in addition to the regulation of cardiac beta-receptors by thyroid hormone that has been described previously, thyroid hormone exerts a regulatory effect on the characteristics of cardiac alpha-receptors as well. These changes provide a possible molecular mechanism for the thyroid hormone-induced alterations in cardiac responsiveness to alpha-adrenergic stimulation that have been reported previously. © Lippincott-Raven Publishers.