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 microg/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 microg/ml) were not prevented by atropine (1 microg/ml) and 3,7-dimethyl-1-propargylxanthine (DMPX; 1.5 microg/ml), an adenosine A(2) receptor antagonist, but 1,3-dipropargyl-8-cyclopentylxanthine (DPCPX;12 microg/ml), a specific adenosine A(1) receptor antagonist significantly blocked these effects (P < 0.001) and theophylline (30 microg/ml) a non- selective adenosine A(1)/A(2A) 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 A(1) receptor mechanism.