Dexmedetomidine Modulates Histamine-induced Ca<sup>2+</sup> Signaling and Pro-inflammatory Cytokine Expression
Dexmedetomidine Modulates Histamine-induced Ca<sup>2+</sup> Signaling and Pro-inflammatory Cytokine Expression
- Dongki Yang Jeong Hee Hong
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제19권 제5호
- 등재여부 : KCI등재
- 2015.01
- 413 - 420 (8 pages)
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<sup>2+</sup> release and subsequent mediate or progress inflammation. Dexmedetomidine has been reported to exert inhibitory effect on inflammation both <i>in vitro</i> and <i>in vivo</i> 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<sup>2+</sup> 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<sup>2+</sup> peak or increase in the presence or absence of external Ca<sup>2+</sup>. When cells were stimulated with histamine after pretreatment with various concentrations of dexmedetomidine, we observed inhibited histamine-induced [Ca<sup>2+</sup>]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<sup>2+</sup> signaling and IL-6 expression and will be useful for understanding the antagonistic properties of dexmedetomidine on histamine-induced signaling beyond its sedative effect.