title: The role of adenosine receptors on amitriptyline-induced electrophysiological changes on rat atrium.
abstract: We investigated the role of adenosine receptors in amitriptyline-induced cardiac action potential (AP) changes in isolated rat atria. In the first group, APs were recorded after cumulative addition of amitriptyline (1 μM, 10 μM and 50 μM). In other groups, each atrium was incubated with selective adenosine A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 10(-4) M) or selective adenosine A(2a) receptor antagonist (8-(3-chlorostyryl) caffeine, 10(-5) M) before amitriptyline administration. Resting membrane potential, AP amplitude (APA), AP duration at 50% and 80% of repolarization (APD(50) and APD(80), respectively), and the maximum rise and decay slopes of AP were recorded. Amitriptyline (50 μM) prolonged the APD(50) and APD(80) (p < 0.001) and the maximum rise slope of AP was reduced by amitriptyline (p < 0.0001). Amitriptyline reduced maximum decay slope of AP only at 50 μM (p < 0.01). DPCPX significantly decreased the 50-μM amitriptyline-induced APD(50) and APD(80) prolongation (p < 0.001). DPCPX significantly prevented the effects of amitriptyline (1 μM and 50 μM) on maximum rise slope of AP (p < 0.05). DPCPX significantly prevented the amitriptyline-induced (50 μM) reduction in maximum decay slope of AP (p < 0.001). The selective adenosine A(1) receptor antagonist prevented the electrophysiological effects of amitriptyline on atrial AP. A(1) receptor stimulation may be responsible for the cardiovascular toxic effects produced by amitriptyline.
authors.affiliation: Department of Pharmacology, School of Medicine, Dokuz Eylul University, Inciralti, Izmir, Turkey. sule.kalkan@deu.edu.tr
authors.forename: S
authors.initials: S
authors.lastname: Kalkan
authors.forename: K
authors.initials: K
authors.lastname: Oransay
authors.forename: I B
authors.initials: IB
authors.lastname: Bal
authors.forename: M
authors.initials: M
authors.lastname: Ertunc
authors.forename: Y
authors.initials: Y
authors.lastname: Sara
authors.forename: A B
authors.initials: AB
authors.lastname: Iskit
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D055724:Electrophysiological Phenomena; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000502:physiology*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D018047:Receptors, Purinergic P1; D000639:Amitriptyline