Inhibitory effects of desmethylimipramine on the action of thyroxine on cardiac beta-receptors and myocardial phosphorylase.
The influence of chronic administration of desmethylimipramine (DMI) on the actions of thyroxine (T4) on rat heart was studied. Administration od DMI (10 mg/kg, i.p., twice daily) for 7 days did not alter the cardiac beta-adrenergic receptor density or the affinity for (-)[3H]dihydroalprenolol (3H-DHA) but diminished the activation of myocardial phosphorylase produced by isoproterenol. Chronic injections of T4 (500 microgram/rat) for 5 days caused an increase in the number of beta-adrenergic receptors in the heart and potentiated the stimulatory effect of isoproterenol on cardiac phosphorylase alpha activity. When DMI was administered concomitantly with T4, there was no increase in the density of myocardial beta-adrenergic receptors and the T4-induced potentiation of the activation of heart phosphorylase by isoproterenol was abolished. However, simultaneous treatment of the rats with DMI and TR4 did not diminish the positive chronotropic effect of T4. It was concluded that DMI, while not affecting the population of cardiac beta-adrenergic receptors by itself, prevents the increase in these receptors produced by T4 and obviates the T4-induced potentiation of phosphorylase activation by isoproterenol. That the tachycardia caused by T4 persists in hearts in which DMI has impeded the increase in myocardial beta-receptors suggests that the increase in heart rate is not dependent on cardiac beta-adrenergic receptor density.
D000818:Animals; D001665:Binding Sites; D003891:Desipramine / Q000494:pharmacology*; D004082:Dihydroalprenolol / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000032:analysis* / Q000201:enzymology; D010762:Phosphorylase a / Q000032:analysis*; D006005:Phosphorylases / Q000032:analysis*; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*; D013974:Thyroxine / Q000494:pharmacology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D010762:Phosphorylase a; D006005:Phosphorylases; D007545:Isoproterenol; D013974:Thyroxine; D003891:Desipramine