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Journal Article 2011; 32(4): 552-556 PubMed PMID: 21876510 Citation  Keywords:  Adrenergic Agents:pharmacology, Adrenergic alpha-2 Receptor Agonists:pharmacology, Animals, Dexmedetomidine:pharmacology, Drug Synergism, Drug Therapy, Combination, Ephedrine:pharmacology, Female, Male, Mice, Motor Activity:drug effects, Nociceptors:drug .   

OBJECTIVES: Dexmedetomidine, a highly selective alpha-2-adrenoceptor agonist, was recently introduced into clinical practice for its sedative and analgesic properties. The purpose of this study was to evaluate whether the psychostimulant drug ephedrine has any effect on dexmedetomidine-induced antinociception and locomotor inhibitor activity in mice in acute application.

METHODS: In both sexes of swiss albino mice; antinociception was assessed with hot-plate test and the locomotor, exploratory activities were assessed with holed open field test. The animals were received; saline + saline, ephedrine (10 mg/kg) + saline, saline + dexmedetomidine (15 μg/kg) and ephedrine (10 mg/kg) + dexmedetomidine (15 μg/kg), intraperitoneally, 30 min before hot plate or holed open field tests.

RESULTS: In the hot plate test in mice, co-administration of 15 μg/kg dexmedetomidine with 10 mg/kg ephedrine intraperitoneally not only enhanced, but also prolonged the duration of antinociception induced by dexmedetomidine. At the same time, the locomotor inhibitory effect of dexmedetomidine was counteracted by ephedrine.

CONCLUSION: We concluded that the combined administration of dexmedetomidine with ephedrine may have beneficial effects in the treatment of pain without causing sedation, which limits the use of dexmedetomidine as an analgesic in humans....

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Journal Article 2010; 31(5): 635-644 PubMed PMID: 21173746 Citation  Keywords:  Adrenergic alpha-1 Receptor Agonists:pharmacology, Adrenergic alpha-1 Receptor Antagonists:pharmacology, Adrenergic alpha-2 Receptor Agonists:pharmacology, Adrenergic alpha-2 Receptor Antagonists:pharmacology, Animals, Clonidine:pharmacology, Cytotoxicity.   

OBJECTIVE: Our previous work has shown that α-adrenoreceptor (α-AR)-coupled signaling modulates T lymphocyte function. Here, we investigate the expression of α₁- and α₂-ARs in natural killer (NK) cells and roles of the two subtypes of α-ARs and their coupled signals in modulation of NK cell function.

METHODS: NK cells were purified by Ficoll-Isopaque one-step gradient centrifugation and in discontinuous Percoll density gradients from splenic cells of rats. The mRNA expressions of α₁-ARs and α₂-ARs in NK cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometry was employed to detect the cytotoxicity of NK cells.

RESULTS: NK cells expressed both α₁-AR and α₂-AR mRNAs. Phenylephrine, a selective α₁-AR agonist, increased the cytotoxicity of NK cells. This effect of phenylephrine was reduced by corynanthine, a selective α₁-AR antagonist, and was blocked by PLC inhibitor U-73122, but not by PKA inhibitor H-89. Clonidine, a selective α₂-AR agonist, also enhanced the cytotoxicity of NK cells. This action of clonidine was blocked by α₂-AR antagonist yohimbine or by PKA inhibitor H-89, but not by PLC inhibitor U-73122.

CONCLUSIONS: NK cells express α₁- and α₂-ARs. Activation of the either subtype of α-ARs augments NK cell function. This action of α₁-ARs is transduced by PLC, while α₂-AR effect is mediated by PKA signaling....

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