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.Základní údaje
Originální název
Disruption of dopamine D1/D2 receptor complex is involved in the function of haloperidol in cardiac H9c2 cells
Autoři
LENCESOVA, L. (703 Slovensko), Ivan SZADVÁRI (703 Slovensko, domácí), Petr BABULA (203 Česká republika, domácí), J. KUBICKOVA (703 Slovensko), B. CHOVANCOVA (703 Slovensko), K. LOPUSNA (703 Slovensko), I. REZUCHOVA (703 Slovensko), Zuzana NOVÁKOVÁ (203 Česká republika, domácí), Oľga KRIŽANOVÁ (703 Slovensko, domácí) a Marie NOVÁKOVÁ (203 Česká republika, garant, domácí)
Vydání
Life Sciences, Amsterdam, Elsevier, 2017, 0024-3205
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
30104 Pharmacology and pharmacy
Stát vydavatele
Nizozemské království
Utajení
není předmětem státního či obchodního tajemství
Impakt faktor
Impact factor: 3.234
Kód RIV
RIV/00216224:14110/17:00095195
Organizační jednotka
Lékařská fakulta
UT WoS
000414376500025
Klíčová slova anglicky
Haloperidol; Dopamine D2 receptor; D1R/D2R heterodimeric complex; H9c2 cell line
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 20. 3. 2018 12:52, Soňa Böhmová
Anotace
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.
Návaznosti
GAP102/12/2034, projekt VaV |
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MUNI/A/1355/2016, interní kód MU |
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MUNI/A/1365/2015, interní kód MU |
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