Catecholamine-thyroid hormone interaction on myocardial ornithine decarboxylase.
Myocardial phosphorylase alpha activity responds to stimulation by catecholamines and thyroid hormone. In hyperthyroidism this enzyme is supersensitive to beta-adrenergic stimulation and blockade, indicating that its increased activity is an indirect effect of thyroid hormone. Myocardial ornithine decarboxylase (ODC) activity also responds to catecholamine and thyroid hormone stimulation. In the present studies, we sought to determine whether ODC shares the responses of phosphorylase alpha in hyperthyroidism. As opposed to euthyroid rats, isoproterenol acutely inhibited myocardial OCD activity in hyperthyroid rats. Timolol (60 mg/kg) injected immediately before the isoproterenol blocked this paradoxical inhibitory effect, defining it as beta-adrenergic. When timolol (100 mg/kg), distributed over a 24-h period, was administered during the 3 days of triiodothyronine (T3) administration, it blocked the T3 stimulation of myocardial OCD activity by 35%. However, timolol affected weight gain of the hyperthyroid rats. When fasted rats were used, timolol was without effect on T3-induced myocardial ODC stimulation. Timolol was also without effect on T3-induced stimulation of hepatic ODC or on T3-induced cardiomegaly. Timolol did decrease the T3-induced tachycardia. In summary, in the hyperthyroid heart, 1) isoproterenol paradoxically inhibits myocardial ODC activity and 2) timolol, when food intake is not a variable, is without effect. We conclude that the effect of thyroid hormone on myocardial ODC is not mediated by change in catecholamine sensitivity. Thus the behavior of phosphorylase alpha does not represent a general enzymatic phenomenon.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002262:Carboxy-Lyases / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D006980:Hyperthyroidism / Q000201:enzymology*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009929:Organ Size / Q000187:drug effects; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013999:Timolol / Q000494:pharmacology*
D011412:Propanolamines; D013999:Timolol; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D007545:Isoproterenol