The objectives of the proposed studies are to: 1) study the effects of drugs and hormones on the number and binding characteristics of beta adrenergic and muscarinic cholinergic receptors in the heart to determine the relationship between changes in these receptors to alterations in cardiac function and metabolism; 2) measure the choline uptake in synaptosomes made from brains from normal rats and in synaptosomes from rats pretreated with thyroxine, desmethylimipramine (DMI) and with DMI plus thyroxine; 3) elucidate the effect of DMI in preventing the development of thyroxine-induced increase in cardiac adrenergic beta receptors. Alterations in myocardial metabolism will be measured by determining cardiac cyclic AMP, phosphorylase a activity and in some experiments, phosphorylase b kinase activity will be measured. Mechanical functions of the heart will be assessed by monitoring heart rate and force of contraction in either the open-chest rat preparation or with the isolated, perfused rat heart. The density and affinity characteristics of beta adrenergic and muscarinic cholinergic receptors in heart membrane preparations will be determined by measuring (3H)-dihydroalprenolol binding for beta receptors and (3H)-quinuclidinyl benzilate binding for cholinergic receptors.