Alterations in the cardiac adenylate cyclase activity in hypothyroid rat

Adenylate cyclase activity of the washed particles from the ventricles of rats made hypothyroid by propylthiouracil (P.T.U.) treatment was studied in the absence or presence of different concentrations of catecholamines, guanylimido-diphosphate (GppNHp) and NaF. The washed particles preparation of hypothyroid rat displayed higher basal adenylate cyclase activity in comparison to that in the euthyroid animal. Fluoride stimulation was unaltered but GppNHp stimulation was markedly depressed over a wide range of concentrations in the hypothyroid heart washed particles. Epinephrine stimulation in the presence of GppNHp was altered only at 10(-5) to 10(-4)M concentrations. Depressed responsiveness of cardiac adenylate cyclase to GppNHp and epinephrine was also found in washed particles of thyroidectomized rats. Depression of GppNHp or epinephrine response in hypothyroid animals was reversed 48 hours after T3 administration. In contrast to the washed particulate preparation, no depressions in the responses of adenylate cyclase to GppNHp or epinephrine were seen in the purified sarcolemmal membranes from P.T.U. induced hypothyroid or thyroidectomized rat hearts. It is proposed that altered guanine nucleotide binding or altered guanine nucleotide binding protein-catalytic subunit interaction in the adenylate cyclase system may be an underlying mechanism of depressed positive inotropic action of catecholamines in the hypothyroid state.