Effects of phenylephrine and isoproterenol on the activity of cyclic AMP-dependent protein kinase of hypothyroid rat tissues.

Abstract

Abstract-The present study was designed to examine the properties of cyclic AMP dependent protein kinase from normal and hypothyroid rat tissues. The activity of the liver enzyme decreased in hypothyroid rats and this reduced activity may be due to the decrease in synthesis of enzyme protein. The enzyme activity from the kidney of hypothyroid rats increased by 35% in the absence of cyclic AMP. Further, the enzyme from the kidney of hypothyroid animals responded to phenylephrine and isoproterenol.In the heart, the basal enzyme activity was the same in both groups, but the enzyme from the heart of hypothyroid animals did not respond to isoproterenol. When hypothyroid rats were treated with 3,3',5-triiodothyronine, the enzyme activities from those rat tissues showed essentially the same level as those of the corresponding normal ones. These results suggest that thyroid hormone regulates adrenergic agonists mediated responses both at the sites of adrenoceptors and that of protein phosphory lation. Furthermore, the dependence on thyroid hormone varies according to the tissue.Thyroid hormone plays an important role in the regulation of adrenergic agonists mediated responses in tissues from several species (1). There may be at least two sites of action of thyroid hormone in regard to this mechanism: one is the adrenoceptors including adenylate cyclase and the other the intracellular processes after the formation of the agonists receptor complex.In our laboratory, we found that the increased response of a-adrenoceptors of hearts from hypothyroid rats to phenylephrine and decreased response of jj-adrenoceptors of hearts and livers from hypothyroid rats to isoproterenol could not be explained by changes in intracellular contents of cyclic AMP. It has also been suggested that the decreased sensitivity of i3-adrenoceptor in the liver and heart might account for the change in enzyme activities involved in cyclic AMP metabolism (2-5).The present study was carried out to compare the cyclic AMP-dependent protein kinase activity of normal and hypothyroid rats and to examine the effects of adrenergic agonists on this enzyme. The possible physiological relationship between thyroid hormone and adrenergic agonists is discussed. MATERIALS AND METHODSMale Wistar strain rats were used throughout the experiments. Rats were made hypo

Effect of hypothyroid status on adenosine 3',5'-monophosphate-dependent protein kinase of rat kidney.

“…Male Wistar rats were fed a 0.15% PTU diet for over 12 weeks. The hypothyroid status obtained during this period was as reported earlier (6).…”

“…We found that the activity of cyclic AMP dependent protein kinase from hypothyroid kidneys increased as compared with findings in normal kidneys (6).…”

Effect of thyroid hormone on cyclic AMP phosphodiesterase in rat kidney.

“…Concentrations of L-3,5,3'-triiodothyronine (T3) and thyroxine in the serum markedly decreased in these rats, as described previously (16). Hypothyroid rats were given 50 ,€g of T3 per 100 g body weight s.c., daily x 3 and sacrificed 48 h after the last administration of T3.…”