A POSSIBLE NONSPECIFIC SITE OF ACTION OF AMIODARONE ON NEWBORN RAT-HEART CELL IN CULTURE

Amiodarone and its major metabolite desethylamiodarone are potent anti arrhythmic drugs that have multiple pharmacological effects on the hea rt. We examined the effect of both drugs on the neonatal rat heart mon olayer cell culture. The cells were stimulated with L-arterenol (10(-7 )M) and choleratoxin(1.5 mu g/ml). Both the spontaneous pulsation rate and intracellular cAMP level were followed. Amiodarone(10(-7)M) or de sethylamiodarone (10(-7)M), incorporated into phosphatidylcholine vesi cles, decreased the stimulated cell pulsation rate 3 min after additio n of drugs, and the level of intracellular cAMP 30 min after addition as well. Propranolol (10(-7)M) had no further effect on the pulsation rate after 3 min. In the presence of amiodarone and propranolol the st imulation of L-arterenol was completely abolished and both the pulsati on rate and cAMP level proved to be lower than the control values. The stimulation of choleratoxin on pulsation rate was also decreased by a ddition of amiodarone and the cAMP level was lowered after 30 min as w ell. Desethylamiodarone exhibited similar behavior to amiodarone altho ugh it proved to be less effective. It is unlikely that amiodarone and desethylamiodarone act on beta-adrenergic receptors in a competitive manner. Our data suggests that amiodarone and its metabolite could act in a nonspecific manner perturbing the hydrophobic interaction in the cell membrane and thereby decoupling the receptor or the nucleotide r egulator protein and adenylate cyclase.