title: The role of adenosine receptors and endogenous adenosine in citalopram-induced cardiovascular toxicity.
abstract: OBJECTIVE
  We investigated the role of adenosine in citalopram-induced cardiotoxicity.
  
  
  METHODS
  Protocol 1: Rats were randomized into four groups. Sodium cromoglycate was administered to rats. Citalopram was infused after the 5% dextrose, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; A1 receptor antagonist), 8-(-3-chlorostyryl)-caffeine (CSC; A2a receptor antagonist), or dimethyl sulfoxide (DMSO) administrations. Protocol 2: First group received 5% dextrose intraperitoneally 1 hour prior to citalopram. Other rats were pretreated with erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA; inhibitor of adenosine deaminase) and S-(4-Nitrobenzyl)-6-thioinosine (NBTI; inhibitor of facilitated adenosine transport). After pretreatment, group 2 received 5% dextrose and group 3 received citalopram. Adenosine concentrations, mean arterial pressure (MAP), heart rate (HR), QRS duration and QT interval were evaluated.
  
  
  RESULTS
  In the dextrose group, citalopram infusion caused a significant decrease in MAP and HR and caused a significant prolongation in QRS and QT. DPCPX infusion significantly prevented the prolongation of the QT interval when compared to control. In the second protocol, citalopram infusion did not cause a significant change in plasma adenosine concentrations, but a significant increase observed in EHNA/NBTI groups. In EHNA/NBTI groups, citalopram-induced MAP and HR reductions, QRS and QT prolongations were more significant than the dextrose group.
  
  
  CONCLUSIONS
  Citalopram may lead to QT prolongation by stimulating adenosine A1 receptors without affecting the release of adenosine.
authors.affiliation: Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey.
authors.forename: Kubilay
authors.initials: K
authors.lastname: Oransay
authors.affiliation: Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey.
authors.forename: Nil
authors.initials: N
authors.lastname: Hocaoglu
authors.affiliation: Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey.
authors.forename: Mujgan
authors.initials: M
authors.lastname: Buyukdeligoz
authors.affiliation: Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey.
authors.forename: Yesim
authors.initials: Y
authors.lastname: Tuncok
authors.affiliation: Department of Pharmacology, Dokuz Eylul University, School of Medicine, Inciralti, Izmir, Turkey.
authors.forename: Sule
authors.initials: S
authors.lastname: Kalkan
mesh_terms: D000241:Adenosine / Q000097:blood / Q000378:metabolism*; D000818:Animals; D066126:Cardiotoxicity; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism*; D015283:Citalopram / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000633:toxicity*
chemical_list: D000241:Adenosine; D015283:Citalopram; D018047:Receptors, Purinergic P1; D017367:Selective Serotonin Reuptake Inhibitors
keywords: Adenosine receptor; QT prolongation; citalopram toxicity; endogenous adenosine; rat
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