title: Haloperidol increases expression of the inositol 1,4,5-trisphosphate receptors in rat cardiac atria, but not in ventricles.
abstract: Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias. High affinity binding sites for the prototypical sigma ligand haloperidol were found in membranes of cardiac myocytes from adult rats. Activation of sigma 1 receptor leads to a release of calcium from the endoplasmic reticulum that follows increased synthesis of inositol 1,4,5-trisphosphate (IP3). We studied the effect of long-term haloperidol treatment on the expression of sigma 1 receptors, IP3 receptors of type 1 and 2 in the individual parts of the rat heart, in isolated rat cardiomyocytes and in PC12 cells. We have found that prolonged treatment with haloperidol significantly increased mRNA levels of sigma 1 receptors in both atria and ventricles. Sigma 1 receptor's mRNA was increased also in isolated cardiomyocytes. Haloperidol treatment affects the expression of IP3 receptors of type 1 and 2 in cardiac atria, but not in cardiac ventricles. We observed increase in IP3 receptors in differentiated PC12 cells, but not in isolated cardiomyocytes. We propose that this increase might participate in triggering cardiac arrhythmias during haloperidol treatment, which has to be further verified.
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Komenského nám. 2, Brno, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Novakova
authors.forename: Barbora
authors.initials: B
authors.lastname: Sedlakova
authors.forename: Marta
authors.initials: M
authors.lastname: Sirova
authors.forename: Katerina
authors.initials: K
authors.lastname: Fialova
authors.forename: Olga
authors.initials: O
authors.lastname: Krizanova
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D014150:Antipsychotic Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012333:RNA, Messenger; D006220:Haloperidol