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Dexmedetomidine Modulates Histamine-induced Ca(2+) Signaling and Pro-inflammatory Cytokine Expression.

Yang D, Hong JH - Korean J. Physiol. Pharmacol. (2015)

Bottom Line: Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+).Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine.Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon 406-799, Korea.

ABSTRACT
Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing α2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca(2+) release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca(2+) signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+). When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca(2+)]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

No MeSH data available.


Related in: MedlinePlus

Histamine-induced [Ca2+]i signals were inhibited by dexmedetomidine. (A) Expression levels of histamine receptors mRNA (H1R to H4R) in HeLa cells. (B) Changes in [Ca2+]i induced by 100 nM histamine. (C) Changes in [Ca2+]i after pretreatment with 10 ng/mL dexmedetomidine (Dex) and subsequent treatment with 100 nM histamine. (D) Changes in [Ca2+]i after pretreatment with 10 µM histamine (E) Changes in [Ca2+]i after pretreatment with 100 ng/mL dexmedetomidine and subsequent treatment with 10 µM histamine. The upper bars indicate the extracellular solutions applied to the cells and traces were selected randomly. Three separate experiments were performed and each point represents a mean±SEM. (-): no RNA, M: DNA ladder (bp).
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Figure 2: Histamine-induced [Ca2+]i signals were inhibited by dexmedetomidine. (A) Expression levels of histamine receptors mRNA (H1R to H4R) in HeLa cells. (B) Changes in [Ca2+]i induced by 100 nM histamine. (C) Changes in [Ca2+]i after pretreatment with 10 ng/mL dexmedetomidine (Dex) and subsequent treatment with 100 nM histamine. (D) Changes in [Ca2+]i after pretreatment with 10 µM histamine (E) Changes in [Ca2+]i after pretreatment with 100 ng/mL dexmedetomidine and subsequent treatment with 10 µM histamine. The upper bars indicate the extracellular solutions applied to the cells and traces were selected randomly. Three separate experiments were performed and each point represents a mean±SEM. (-): no RNA, M: DNA ladder (bp).

Mentions: HeLa cells were examined to detect the expression of histamine receptors subtypes H1R through H4R. The specificity of the primers was confirmed by sequencing the gene products. HeLa cells predominantly expressed H1R (Fig. 2A). To examine the modulatory role of dexmedetomidine on histamine, cells were compared with respect to histamine-induced [Ca2+]i oscillations and dexmedetomidine-pretreated histamine-induced [Ca2+]i signals. As shown in Fig. 2B and 2C (54 cells and 49 cells from three independent experiments, respectively), 10 ng/mL dexmedetomidine pretreatment inhibited histamine-induced [Ca2+]i oscillation. Even at histamine concentrations of 10 µM, [Ca2+]i increases were inhibited by the pretreatment with 100 ng/mL dexmedetomidine (Fig. 2D and 2E show 64 and 70 cells from three independent experiments, respectively). These results revealed that dexmedetomidine inhibited the maximal Ca2+ peak and Ca2+ oscillatory patterns.


Dexmedetomidine Modulates Histamine-induced Ca(2+) Signaling and Pro-inflammatory Cytokine Expression.

Yang D, Hong JH - Korean J. Physiol. Pharmacol. (2015)

Histamine-induced [Ca2+]i signals were inhibited by dexmedetomidine. (A) Expression levels of histamine receptors mRNA (H1R to H4R) in HeLa cells. (B) Changes in [Ca2+]i induced by 100 nM histamine. (C) Changes in [Ca2+]i after pretreatment with 10 ng/mL dexmedetomidine (Dex) and subsequent treatment with 100 nM histamine. (D) Changes in [Ca2+]i after pretreatment with 10 µM histamine (E) Changes in [Ca2+]i after pretreatment with 100 ng/mL dexmedetomidine and subsequent treatment with 10 µM histamine. The upper bars indicate the extracellular solutions applied to the cells and traces were selected randomly. Three separate experiments were performed and each point represents a mean±SEM. (-): no RNA, M: DNA ladder (bp).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4553400&req=5

Figure 2: Histamine-induced [Ca2+]i signals were inhibited by dexmedetomidine. (A) Expression levels of histamine receptors mRNA (H1R to H4R) in HeLa cells. (B) Changes in [Ca2+]i induced by 100 nM histamine. (C) Changes in [Ca2+]i after pretreatment with 10 ng/mL dexmedetomidine (Dex) and subsequent treatment with 100 nM histamine. (D) Changes in [Ca2+]i after pretreatment with 10 µM histamine (E) Changes in [Ca2+]i after pretreatment with 100 ng/mL dexmedetomidine and subsequent treatment with 10 µM histamine. The upper bars indicate the extracellular solutions applied to the cells and traces were selected randomly. Three separate experiments were performed and each point represents a mean±SEM. (-): no RNA, M: DNA ladder (bp).
Mentions: HeLa cells were examined to detect the expression of histamine receptors subtypes H1R through H4R. The specificity of the primers was confirmed by sequencing the gene products. HeLa cells predominantly expressed H1R (Fig. 2A). To examine the modulatory role of dexmedetomidine on histamine, cells were compared with respect to histamine-induced [Ca2+]i oscillations and dexmedetomidine-pretreated histamine-induced [Ca2+]i signals. As shown in Fig. 2B and 2C (54 cells and 49 cells from three independent experiments, respectively), 10 ng/mL dexmedetomidine pretreatment inhibited histamine-induced [Ca2+]i oscillation. Even at histamine concentrations of 10 µM, [Ca2+]i increases were inhibited by the pretreatment with 100 ng/mL dexmedetomidine (Fig. 2D and 2E show 64 and 70 cells from three independent experiments, respectively). These results revealed that dexmedetomidine inhibited the maximal Ca2+ peak and Ca2+ oscillatory patterns.

Bottom Line: Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+).Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine.Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, College of Medicine, Gachon University, Incheon 406-799, Korea.

ABSTRACT
Dexmedetomidine is a sedative and analgesic agent that exerts its effects by selectively agonizing α2 adrenoceptor. Histamine is a pathophysiological amine that activates G protein-coupled receptors, to induce Ca(2+) release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both in vitro and in vivo studies. However, it is unclear that dexmedetomidine modulates histamine-induced signaling and pro-inflammatory cytokine expression. This study was carried out to assess how dexmedetomidine modulates histamine-induced Ca(2+) signaling and regulates the expression of pro-inflammatory cytokine genes encoding interleukin (IL)-6 and -8. To elucidate the regulatory role of dexmedetomidine on histamine signaling, HeLa cells and human salivary gland cells which are endogenously expressed histamine 1 receptor were used. Dexmedetomidine itself did not trigger Ca(2+) peak or increase in the presence or absence of external Ca(2+). When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca(2+)]i signal in both cell types. Histamine stimulated IL-6 mRNA expression not IL-8 mRNA within 2 hrs, however this effect was attenuated by dexmedetomidine. Collectively, these findings suggest that dexmedetomidine modulates histamine-induced Ca(2+) signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.

No MeSH data available.


Related in: MedlinePlus