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.
Pousti
Abbas
A
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran. drpousti@yahoo.com
Deemyad
Tara
T
Malihi
Golrokh
G
Brumand
Kaveh
K
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D003864:Depression, Chemical; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
D018687:Antidepressive Agents, Second-Generation; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D005473:Fluoxetine; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine