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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

Dexmedetomidine did not elicit [Ca2+]i signals in HeLa cells. Changes in [Ca2+]i induced by 10 ng/mL dexmedetomidine in (A) 1 mM Ca2+ medium and (B) Ca2+ free medium (0 Ca2+). The upper bars indicate the extracellular solutions applied to the cells.
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Figure 1: Dexmedetomidine did not elicit [Ca2+]i signals in HeLa cells. Changes in [Ca2+]i induced by 10 ng/mL dexmedetomidine in (A) 1 mM Ca2+ medium and (B) Ca2+ free medium (0 Ca2+). The upper bars indicate the extracellular solutions applied to the cells.

Mentions: Dexmedetomidine is a highly selective α2 adrenoceptor agonist and induced aortic contraction via an influx of extracellular Ca2+ [20]. To evaluate the role of dexmedetomidine in Ca2+ signaling, HeLa cells were treated with 10 or 100 ng/mL dexmedetomidine. The application of 10 ng/mL dexmedetomidine did not alter the basal [Ca2+]i level or induce a [Ca2+]i peak in the presence or absence of Ca2+ in the PSS media in HeLa cells (Figs. 1A and 1B, 89 and 102 cells from three independent experiments, respectively) and in HSG cells (data not shown). Even 100 ng/mL dexmedetomidine failed to elicit an intrinsic [Ca2+]i response in HeLa cells (data not shown).


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

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

Dexmedetomidine did not elicit [Ca2+]i signals in HeLa cells. Changes in [Ca2+]i induced by 10 ng/mL dexmedetomidine in (A) 1 mM Ca2+ medium and (B) Ca2+ free medium (0 Ca2+). The upper bars indicate the extracellular solutions applied to the cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Dexmedetomidine did not elicit [Ca2+]i signals in HeLa cells. Changes in [Ca2+]i induced by 10 ng/mL dexmedetomidine in (A) 1 mM Ca2+ medium and (B) Ca2+ free medium (0 Ca2+). The upper bars indicate the extracellular solutions applied to the cells.
Mentions: Dexmedetomidine is a highly selective α2 adrenoceptor agonist and induced aortic contraction via an influx of extracellular Ca2+ [20]. To evaluate the role of dexmedetomidine in Ca2+ signaling, HeLa cells were treated with 10 or 100 ng/mL dexmedetomidine. The application of 10 ng/mL dexmedetomidine did not alter the basal [Ca2+]i level or induce a [Ca2+]i peak in the presence or absence of Ca2+ in the PSS media in HeLa cells (Figs. 1A and 1B, 89 and 102 cells from three independent experiments, respectively) and in HSG cells (data not shown). Even 100 ng/mL dexmedetomidine failed to elicit an intrinsic [Ca2+]i response in HeLa cells (data not shown).

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