Involvement of adenosine in the effect of fluoxetine on isolated guinea-pig atria

The effect of fluoxetine (FL) a selective serotonin reuptake inhibitor antidepressant was studied on the rate and force of contractions of isolated guinea-pig atria. FL (2–16 μg/ml) caused a decrease in the rate (13–45%) and contractile force (41–53%) of isolated guinea-pig atria in a dose-dependent manner. These negative inotropic and chronotropic effect of FL (4 μg/ml) were not prevented by atropine (1 μg/ml) and 3,7-dimethyl-1-propargylxanthine (DMPX; 1.5 μg/ml), an adenosine A2 receptor antagonist, but 1,3-dipropargyl-8-cyclopentylxanthine (DPCPX;12 μg/ml), a specific adenosine A1 receptor antagonist significantly blocked these effects (P < 0.001) and theophylline (30 μg/ml) a non- selective adenosine A1/A2A receptor antagonist also prevented the inotropic and chronotropic effects of FL. These results suggest that the negative chronotropic and inotropic effect of FL on isolated guinea-pig atria is probably mediated through an inhibition of the reuptake of adenosine or the A1 receptor mechanism.