Disruption of dopamine D1/D2 receptor complex is involved in
the function of haloperidol in cardiac H9c2 cells

J 2017

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells

LENCESOVA, L., Ivan SZADVÁRI, Petr BABULA, J. KUBICKOVA, B. CHOVANCOVA et. al.

Basic information

Original name

Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells

Authors

LENCESOVA, L. (703 Slovakia), Ivan SZADVÁRI (703 Slovakia, belonging to the institution), Petr BABULA (203 Czech Republic, belonging to the institution), J. KUBICKOVA (703 Slovakia), B. CHOVANCOVA (703 Slovakia), K. LOPUSNA (703 Slovakia), I. REZUCHOVA (703 Slovakia), Zuzana NOVÁKOVÁ (203 Czech Republic, belonging to the institution), Oľga KRIŽANOVÁ (703 Slovakia, belonging to the institution) and Marie NOVÁKOVÁ (203 Czech Republic, guarantor, belonging to the institution)

Edition

Life Sciences, Amsterdam, Elsevier, 2017, 0024-3205

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 3.234

RIV identification code

RIV/00216224:14110/17:00095195

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1016/j.lfs.2017.10.026

UT WoS

000414376500025

Keywords in English

Haloperidol; Dopamine D2 receptor; D1R/D2R heterodimeric complex; H9c2 cell line

Abstract

V originále

Aims: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. Materials and methods: We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. Key findings: We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Significance: Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP3R1 activity, which in turn may account for the increase expression of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect.

Links

GAP102/12/2034, research and development project

Name: Analýza vztahu mezi elektrickými ději a průtokem krve u srdečních komor

Investor: Czech Science Foundation

MUNI/A/1355/2016, interní kód MU

Name: Kardiovaskulární systém očima molekulární fyziologie

Investor: Masaryk University, Category A

MUNI/A/1365/2015, interní kód MU

Name: Kardiovaskulární systém: od modelu přes terapii k prevenci (Acronym: KAMOTEPRE)

Investor: Masaryk University, Category A

Citovat

LENCESOVA, L., Ivan SZADVÁRI, Petr BABULA, J. KUBICKOVA, B. CHOVANCOVA, K. LOPUSNA, I. REZUCHOVA, Zuzana NOVÁKOVÁ, Oľga KRIŽANOVÁ and Marie NOVÁKOVÁ. Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells. Life Sciences. Amsterdam: Elsevier, 2017, vol. 191, DEC 15 2017, p. 186-194. ISSN 0024-3205. Available from: https://dx.doi.org/10.1016/j.lfs.2017.10.026.

@article{1396261,
   author = {Lencesova, L. and Szadvári, Ivan and Babula, Petr and Kubickova, J. and Chovancova, B. and Lopusna, K. and Rezuchova, I. and Nováková, Zuzana and Križanová, Oľga and Nováková, Marie},
   article_location = {Amsterdam},
   article_number = {DEC 15 2017},
   doi = {http://dx.doi.org/10.1016/j.lfs.2017.10.026},
   keywords = {Haloperidol; Dopamine D2 receptor; D1R/D2R heterodimeric complex; H9c2 cell line},
   language = {eng},
   issn = {0024-3205},
   journal = {Life Sciences},
   title = {Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells},
   volume = {191},
   year = {2017}
}

TY  - JOUR
ID  - 1396261
AU  - Lencesova, L. - Szadvári, Ivan - Babula, Petr - Kubickova, J. - Chovancova, B. - Lopusna, K. - Rezuchova, I. - Nováková, Zuzana - Križanová, Oľga - Nováková, Marie
PY  - 2017
TI  - Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells
JF  - Life Sciences
VL  - 191
IS  - DEC 15 2017
SP  - 186-194
EP  - 186-194
PB  - Elsevier
SN  - 00243205
KW  - Haloperidol
KW  - Dopamine D2 receptor
KW  - D1R/D2R heterodimeric complex
KW  - H9c2 cell line
N2  - Aims: Haloperidol is an antipsychotic agent and acts as dopamine D2 receptor (D2R) antagonist, as a prototypical ligand of sigma1 receptors (Sig1R) and it increases expression of type 1 IP3 receptors (IP3R1). However, precise mechanism of haloperidol action on cardiomyocytes through dopaminergic signaling was not described yet. This study investigated a role of dopamine receptors in haloperidol-induced increase in IP3R1 and Sig1R, and compared physiological effect of melperone and haloperidol on basic heart parameters in rats. Materials and methods: We used differentiated NG-108 cells and H9c2 cells. Gene expression, Western blot and immunofluorescence were used to evaluate haloperidol-induced differences; proximity ligation assay (PLA) and immunoprecipitation to determine interactions of D1/D2 receptors. To evaluate cardiac parameters, Wistar albino male rats were used. Key findings: We have shown that antagonism of D2R with either haloperidol or melperone results in upregulation of both, IP3R1 and Sig1R, which is associated with increased D2R, but reduced D1R expression. Immunofluorescence, immunoprecipitation and PLA support formation of heteromeric D1/D2 complexes in H9c2 cells. Treatment with haloperidol (but not melperone) caused decrease in systolic and diastolic blood pressure and significant increase in heart rate. Significance: Because D1R/D2R complexes can engage Gq-like signaling in other experimental systems, these results are consistent with the possibility that disruption of D1R/D2R complex in H9c2 cells might cause a decrease in IP3R1 activity, which in turn may account for the increase expression of IP3R and Sig1R. D2R is probably not responsible for changes in cardiac parameters, since melperone did not have any effect.
ER  -

LENCESOVA, L., Ivan SZADVÁRI, Petr BABULA, J. KUBICKOVA, B. CHOVANCOVA, K. LOPUSNA, I. REZUCHOVA, Zuzana NOVÁKOVÁ, Oľga KRIŽANOVÁ and Marie NOVÁKOVÁ. Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells. \textit{Life Sciences}. Amsterdam: Elsevier, 2017, vol.~191, DEC 15 2017, p.~186-194. ISSN~0024-3205. Available from: https://dx.doi.org/10.1016/j.lfs.2017.10.026.

Detailed Information on Publication Record