Effect of imipramine and desipramine on adenosine receptors in isolated rat atria

  The effect of different doses (1-50 µ M) of imipramine (IMI) and desipramine (DES) on the rate and force of contraction of isolated rat atria was studied. IMI and DES produced a dose-dependent increase in force of contraction (31- 94% for IMI and 35-118% for DES). Pretreatment of rats with reserpine (5 mg/kg) on the isolated atria with propranolol (1 µ g) inhibited the positive ionotropic effect of both drugs. The two antidepressants IMI and DES showed a dose-dependent decrease in rate of contractions (19-87% and 16-88%, respectively). The positive ionotropic and negative chronotropic effects induced by these drugs was significantly prevented by a selective A1 antagonist (DPCPX, 3 µ M). The effects of IMI (5 µ M) and DES (5 µ M) the rate and contractile force was inhibited by atropine (10 nM). The selective A2 antagonist (DMPX, 1.5 µ M) prevented the ionotropic effect produced by IMI and DES. We conclude that in rat atria, the positive ionotropic action of IMI and DES is due to their action on adrenergic, muscarinic, adenosine A1 and A2 receptors, and Ca2+ influx or release from intracellular storages of the rat myocytes. The negative chronotropic action of these two drugs is probably due to the involvement of adenosine A1 receptors and cholinergic mechanisms.