Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F15%3A00063456" target="_blank" >RIV/00159816:_____/15:00063456 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14110/15:00083475

Výsledek na webu

<a href="https://www.jstage.jst.go.jp/article/tjem/236/3/236_199/_pdf" target="_blank" >https://www.jstage.jst.go.jp/article/tjem/236/3/236_199/_pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1620/tjem.236.199" target="_blank" >10.1620/tjem.236.199</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Long-Term Haloperidol Treatment Prolongs QT Interval and Increases Expression of Sigma 1 and IP3 Receptors in Guinea Pig Hearts

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

<a href="/cs/project/ED1.100%2F02%2F0123" target="_blank" >ED1.100/02/0123: Fakultní nemocnice u sv. Anny v Brně - Mezinárodní centrum klinického výzkumu (FNUSA - ICRC)</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Tohoku Journal Of Experimental Medicine

ISSN

0040-8727

e-ISSN

—

Svazek periodika

236

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

JP - Japonsko

Počet stran výsledku

9

Strana od-do

199-207

Kód UT WoS článku

000358823400006

EID výsledku v databázi Scopus

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