Long-term haloperidol treatment prolongs QT interval and
increases expression of sigma 1 and IP3 receptors in guinea pig
hearts

J 2015

Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts

STRAČINA, Tibor, Iva SLANINOVÁ, Hana POLANSKÁ, Martina AXMANOVÁ, Veronika OLEJNÍČKOVÁ et. al.

Basic information

Original name

Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts

Authors

STRAČINA, Tibor (703 Slovakia, guarantor, belonging to the institution), Iva SLANINOVÁ (203 Czech Republic, belonging to the institution), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Martina AXMANOVÁ (203 Czech Republic, belonging to the institution), Veronika OLEJNÍČKOVÁ (203 Czech Republic, belonging to the institution), Petr KONEČNÝ (203 Czech Republic, belonging to the institution), Michal MASAŘÍK (203 Czech Republic, belonging to the institution), Olga KRIZANOVA (703 Slovakia) and Marie NOVÁKOVÁ (203 Czech Republic)

Edition

Tohoku Journal of Experimental Medicine, Miyagi, Tohoku University Medical Press, 2015, 0040-8727

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30105 Physiology

Country of publisher

Japan

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 1.287

RIV identification code

RIV/00216224:14110/15:00083475

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1620/tjem.236.199

UT WoS

000358823400006

Keywords in English

Guinea pig; Haloperidol; Heart; QT prolongation; Sigma 1 receptor

Abstract

V originále

Find fulltext at Masaryk University(opens in a new window)|View at Publisher| Export | Download | More... Tohoku Journal of Experimental Medicine Volume 236, Issue 3, 19 June 2015, Pages 199-207 Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts (Article) Stracina, T.a, Slaninova, I.b, Polanska, H.c, Axmanova, M.c, Olejnickova, V.a, Konecny, P.d, Masarik, M.c, Krizanova, O.e, Novakova, M.af a Department of Physiology, Masaryk University, Brno, Czech Republic b Department of Biology, Masaryk University, Brno, Czech Republic c Department of Pathological Physiology, Masaryk University, Brno, Czech Republic d Department of Physiotherapy and Rehabilitation, Masaryk University, Brno, Czech Republic e Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia f International Clinical Research Center, Animal Center, St. Anne’s Faculty Hospital, Brno, Czech Republic View additional affiliations View references (47) Abstract Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.

Links

MUNI/A/1326/2014, interní kód MU

Name: Kardiovaskulární systém od buňky k lůžku pacienta (Acronym: KASBUNPAC)

Investor: Masaryk University, Category A

Citovat

STRAČINA, Tibor, Iva SLANINOVÁ, Hana POLANSKÁ, Martina AXMANOVÁ, Veronika OLEJNÍČKOVÁ, Petr KONEČNÝ, Michal MASAŘÍK, Olga KRIZANOVA and Marie NOVÁKOVÁ. Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts. Tohoku Journal of Experimental Medicine. Miyagi: Tohoku University Medical Press, 2015, vol. 236, No 3, p. 199-207. ISSN 0040-8727. Available from: https://dx.doi.org/10.1620/tjem.236.199.

@article{1307015,
   author = {Stračina, Tibor and Slaninová, Iva and Polanská, Hana and Axmanová, Martina and Olejníčková, Veronika and Konečný, Petr and Masařík, Michal and Krizanova, Olga and Nováková, Marie},
   article_location = {Miyagi},
   article_number = {3},
   doi = {http://dx.doi.org/10.1620/tjem.236.199},
   keywords = {Guinea pig; Haloperidol; Heart; QT prolongation; Sigma 1 receptor},
   language = {eng},
   issn = {0040-8727},
   journal = {Tohoku Journal of Experimental Medicine},
   title = {Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts},
   volume = {236},
   year = {2015}
}

TY  - JOUR
ID  - 1307015
AU  - Stračina, Tibor - Slaninová, Iva - Polanská, Hana - Axmanová, Martina - Olejníčková, Veronika - Konečný, Petr - Masařík, Michal - Krizanova, Olga - Nováková, Marie
PY  - 2015
TI  - Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts
JF  - Tohoku Journal of Experimental Medicine
VL  - 236
IS  - 3
SP  - 199-207
EP  - 199-207
PB  - Tohoku University Medical Press
SN  - 00408727
KW  - Guinea pig
KW  - Haloperidol
KW  - Heart
KW  - QT prolongation
KW  - Sigma 1 receptor
N2  - Find fulltext at Masaryk University(opens in a new window)|View at Publisher| Export | Download | More... Tohoku Journal of Experimental Medicine Volume 236, Issue 3, 19 June 2015, Pages 199-207 Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts (Article) Stracina, T.a, Slaninova, I.b, Polanska, H.c, Axmanova, M.c, Olejnickova, V.a, Konecny, P.d, Masarik, M.c, Krizanova, O.e, Novakova, M.af a Department of Physiology, Masaryk University, Brno, Czech Republic b Department of Biology, Masaryk University, Brno, Czech Republic c Department of Pathological Physiology, Masaryk University, Brno, Czech Republic d Department of Physiotherapy and Rehabilitation, Masaryk University, Brno, Czech Republic e Center for Molecular Medicine, Slovak Academy of Sciences, Bratislava, Slovakia f International Clinical Research Center, Animal Center, St. Anne’s Faculty Hospital, Brno, Czech Republic View additional affiliations View references (47) Abstract Haloperidol is a neuroleptic drug used for a medication of various psychoses and deliria. Its administration is frequently accompanied by cardiovascular side effects, expressed as QT interval prolongation and occurrence of even lethal arrhythmias. Despite these side effects, haloperidol is still prescribed in Europe in clinical practice. Haloperidol binds to sigma receptors that are coupled with inositol 1,4,5-trisphosphate (IP3) receptors. Sigma receptors are expressed in various tissues, including heart muscle, and they modulate potassium channels. Together with IP3 receptors, sigma receptors are also involved in calcium handling in various tissues. Therefore, the present work aimed to study the effects of long-term haloperidol administration on the cardiac function. Haloperidol (2 mg/kg once a day) or vehiculum was administered by intraperitoneal injection to guinea pigs for 21 consecutive days. We measured the responsiveness of the hearts isolated from the haloperidol-treated animals to additional application of haloperidol. Expression of the sigma 1 receptor and IP3 receptors was studied by real time-PCR and immunohistochemical analyses. Haloperidol treatment caused the significant decrease in the relative heart rate and the prolongation of QT interval of the isolated hearts from the haloperidol-treated animals, compared to the hearts isolated from control animals. The expression of sigma 1 and IP3 type 1 and type 2 receptors was increased in both atria of the haloperidol-treated animals but not in ventricles. The modulation of sigma 1 and IP3 receptors may lead to altered calcium handling in cardiomyocytes and thus contribute to changed sensitivity of cardiac cells to arrhythmias.
ER  -

STRAČINA, Tibor, Iva SLANINOVÁ, Hana POLANSKÁ, Martina AXMANOVÁ, Veronika OLEJNÍČKOVÁ, Petr KONEČNÝ, Michal MASAŘÍK, Olga KRIZANOVA and Marie NOVÁKOVÁ. Long-term haloperidol treatment prolongs QT interval and increases expression of sigma 1 and IP3 receptors in guinea pig hearts. \textit{Tohoku Journal of Experimental Medicine}. Miyagi: Tohoku University Medical Press, 2015, vol.~236, No~3, p.~199-207. ISSN~0040-8727. Available from: https://dx.doi.org/10.1620/tjem.236.199.

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