• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.779-786
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• 1998

A reversed-phase high-performance liquid chromatogrphy (RP-HPLC) has been developed to analyze the metabolites of arachidonic acid based on the specificities of ultraviolet absorption of these various metabolites and is sensitive to the nanogram level. This procedure makes it possible to extract complex mixtures of eicosanoids efficiently with a single step and to analyze them simultaneously by RP-HPLC from biological samples using octadesylsilyl silica extraction column and $PGB_2$ as an internal standard. The cyclooxygenase products {prostaglandin $(PG)D_2,\;PGE_1,\;PGE_2,\;PGF_{1{\alpha}},\;PGF{2{\alpha}},\;6-keto-PGF_{1{\alpha}},$ and thromboxane $B_2(TXB_2)}$ and lipid peroxidation product, isoprostanes, of arachidonic acid were monitored by one isocratic HPLC system at 195 nm wavelength. The lipoxygenase products ${leukotriene(LT)B_4,\;LTC_4,\;LTD_4,$ and 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE} were measured by another isocratic HPLC system at 280 nm for LTs and 235 nm for HETEs. This method provides a simple and reliable way to extract and assess quantitatively the final arachidonic acid metabolites.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.198-198
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• 1996

Eupatilin은 급성위궤양 모델인 HCl-EtOH model에서 0.3mg/kg에서 50% 억제하였으며 10mg/kg에서 95% 최대효과를 나타내었고, indomethacin model에서는 0.8mg/kg에서 50% 억제하였으며, 10mg/kg에서 97% 최대억제효과를 나타내었다. Cyclooxygenase-1의 활성은 1.7, 5.8$\mu\textrm{g}$/$m\ell$에서 prostaglandin E$_2$와 prostacyclin의 생성을 각각 2배 촉진시켰으나, cyclooxygenase-2에 대한 활성에는 영향을 주지 않았다. FMLP로 활성화시킨 호중구에 대한 활성은 0.6$\mu\textrm{g}$/kg에서 50% 억제하여 oxygen free radical 소거활성을 나타내었고, 반면 xanthine oxidase 및 iron-dependant lipid peroxidation 활성에 대해서는 78.8, 26.9$\mu\textrm{g}$/$m\ell$에서50% 억제를 보였다. 5-lipooxygenase 활성은 2.1$\mu\textrm{g}$/$m\ell$ 에서 염증매개인자인 leukotriene B$_4$ 생성을 50% 억제하였다. 이상의 결과로부터 애엽추출의 항궤양 효과는 prostaglandin의 생성촉진 및 oxygen free radical 과 leukotriene B4와 같은 공격인자의 생성억제 등의 복합적인 작용에 기인하는 것으로 생각된다.

• Clinical and Experimental Pediatrics
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• 제49권6호
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• pp.581-588
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• 2006

Asthma is a chronic inflammation of the airway associated with increased bronchial hyperresponsiveness that leads to recurrent episodes of cough, wheezing, breathless, chest tightness. According the recent studies, repeated airway inflammation leads to structural changes so called 'airway remodeling' and associated with decreased pulmonary function. Airway remodeling begins form the early stage of asthma and the early diagnosis and management is very important to prevent airway remodeling. Medication for asthma can be classified into acute symptom reliever and chronic controller. Short acting beta2 agonist is a well-known reliever that reduced asthma symptoms within minutes. Controllers should be taken daily as a long-term basis to control airway inflammation. Inhaled corticosteroid(ICS) is the most effective controller in current use. However, in some patients ICS monotherapy is not sufficient to control asthma. In those cases, other medications such as long acting beta2 agonist, leukotriene modifier or sustained-release theophylline should be added to ICS, which called Add-on-Therapy. Combination inhaler devices are easy to use. Oral leukotriene modifier has a good compliance especially in children. Finally, as asthma is a chronic disease, the development of on-going partnership among health care professionals, the patients, and the patients' family is necessary for the effective management of asthma.

• Bulletin of the Korean Chemical Society
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• 제28권6호
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• pp.1005-1009
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• 2007

Leukotriene B4 (LTB4) is a potent chemoattractant for leukocytes and considered to be an inflammatory mediator. Human BLT2 (hBLT2) is a low-affinity G-protein coupled receptor for LTB4 and mediates pertussis toxin-sensitive chemotactic cell movement. Here, we dissected the interaction between hBLT2 and G-protein alpha subunits using GST fusion proteins containing intracellular regions of hBLT2 and various Gα protein including Gα i1, Gα i2, Gα i3, Gα s1, Gα o1, and Gα z. Among the tested Gα subunits, Gα i3 showed the highest binding to the third intracellular loop region of hBLT2 with a dissociation constant (KD) of 5.0 × 10?6 M. These results suggest that Gα i3 has the highest affinity to hBLT2, and the third intracellular loop region of hBLT2 is the major component for the interaction with Gα i3.

• Molecules and Cells
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• 제27권4호
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• pp.403-408
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• 2009

Skeletal muscle regeneration is a highly orchestrated process initiated by activation of adult muscle satellite cells. Upon muscle injury, the inflammatory process is always accompanied by muscle regeneration. Leukotriene $B_4$ is one of the essential inflammatory mediators. We isolated and cultured primary satellite cells. RT-PCR showed that myoblasts expressed mRNA for $LTB_4$ receptors BLT1 and BLT2, and $LTB_4$ promoted myoblast proliferation and fusion. Quantitative real-time PCR and immunoblotting showed that $LTB_4$ treatment expedited the expression process of differentiation markers MyoD and M-cadherin. U-75302, a specific BLT1 inhibitor, but not LY2552833, a specific BLT2 inhibitor, blocked proliferation and differentiation of myoblasts induced by $LTB_4$, which implies the involvement of the BLT1 pathway. Overall, the data suggest that $LTB_4$ contributes to muscle regeneration by accelerating proliferation and differentiation of satellite cells.

• The Korean Journal of Physiology and Pharmacology
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• 제1권6호
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• pp.825-830
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• 1997

Leukotrienes(LTs) are hewn to act as a mediator provoking tissue response in inflammation. This finding implicates that LTs also play important roles in the pathogenesis of H, pylori-induced gastritis and gastric ulceration. Rebamipide is being currently used as a therapeutics for gastritis and peptic ulcer, but their mechanisms of action have not been known clearly yet. One possibility is that their therapeutic effects are ascribed to interfering with the H. pylori-induced release of LTs from neutrophils and gastric mucosal cells. In the present study, this possibility was tested using $LTB_4$ as the test material in human neutrophils and Kato III cells(gastric adenoma cells as a substitute for gastric mucosal cells). The release of $LTB_4$ from both neutrophils and Kato III cells was time and H. pylori-dose dependent. The maximum release of $LTB_4$ was induced by neutrophils and Kato III cells when these cells incubated with H. pylori $(4.8{\times}10^8\;cells/ml$ for 30min. But in the presence of rebamipide the release of $LTB_4$ from these cells was suppressed in dose dependent manners. The release was completely suppressed at 1.0 mM of rebamipide in neutrophils and 2.0 mM of this drug in Kato III cells, respectively. We also obtained the results that the release of $LTB_4$ was induced by A23187$(Ca^{2+}\;ionophore)$ and the A23187-induced release was also inhibited by rebamipide. It seems that the machanism of action of rebamipide is through its interaction with the level of intracellular $Ca^{2+}$. In view of the roles of $LTB_4$ in inflammatory reaction and the roles of H. pylori in gastritis and peptic ulcer, the effects of this drug observed in this study may contribute to their therapeutic action in these gastric disorders.

• 대한약리학회지
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• 제31권1호
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• pp.123-133
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• 1995

삼환계 항우울제들은 calmodulin 억제 작용을 갖고 있으며, 칼슘 유입, 산화성 인산화 반응 및 ATPase 활성도를 억제하는 것으로 제시되고 있지만 사람 호중구에서의 기능 표현에 대한 효과는 밝혀져 있지 않다. 본 연구에서는 amitriptyline, imipramine과 doxepine이 superoxide와 $H_2O_2$ 생성, myeloperoxidase 유리, leukotriene $B_4$ 생성과 세포내 칼슘의 상승에 나타나는 효과를 조사하였다. 변성된 IgG에 의하여 활성화된 호중구에서 superoxide와 $H_2O_2$ 생성은 amitriptyline, imipramine과 doxepine에 의하여 억제되었고 EDTA, EGTA, verapamil과 bepredil은 superoxide 생성을 억제하였다. Chlorpromazine, trifluoperazine, staurosporine 및 H-7 또한 superoxide 생성을 억제하였다. PMA에 의한 superoxide 생성은 amitriptyline, imipramine과 doxepine, chlorpromazine과 H-7에 의하여 억제되었다. Amitriptyline, imipramine, chlorpromazine과 trifluoperazine은 변성된 IgG에 의한 myeloperoxidase 유리를 억제하였다. 변성된 IgG에 의하여 활성화된 호중구에서 $LTB_4$와 5-HETE 형성은 amitriptyline, imipramine과 doxepine에 의하여 억제되었다. 변성된 IgG에 의한 세포내 칼슘의 증가는 amitriptyline, imipramine, doxepine, chlorpromazine과 EGTA에 의하여 억제되었고, verapamil은 세포내 칼슘의 증가를 약간 억제하였으나 H-7은 세포내 칼슘의 증가에 영향이 없었다. 이상의 결과로부터 변성된 IgG에 의하여 활성화된 호중구에서의 respiratory burst, myeloperoxidase 유리와 LTB, 생성에 대한 amitriptyline, imipramine과 doxepine의 억제효과는 칼슘동원, calmodulin과 protein kinase C의 억제에 기인할 것으로 추정된다.

• Applied Biological Chemistry
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• 제41권4호
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• pp.261-264
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• 1998

Differently substituted styrylquinoline derivatives (6-9) were synthesized by condensation of quinaldine (1) and corresponding substituted benzaldehydes (2-5). Their relative configuration at C11-C12 and coupling patterns were determined by NMR techniques.

• Journal of Applied Biological Chemistry
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• 제48권2호
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• pp.97-100
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• 2005

Chiral dienophile 5 was synthesized from D-glucose by consecutive diisopropylidenation, partial deprotection, diol cleavage, and Wittig reactions. Under thermal conditions, asymmetric Diels-Alder reaction between chiral dienophile and cyclopentadiene gave four possible chiral norbornenes stereoisomers whose absolute configurations were determined through CADD and NMR.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.23-31
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• 2001

MBST at 4hr and SST at 3hr after oral administration remarkably inhibited histamine release from rat mast cells in a dose-dependent manner. MBST treated GPs failed to show biphasic phenomena which indicated to reduce nasal volume as leukotriene antagonists. Both groups of patients who took MBST and SST for 1 week or 2weeks showed significant decreased symptom severity index(SSI) from treatment week 2(p<0.05). The percent volume change after challenge of the antigen was decreased in patients took the extracts for tweets. We abstained longer suppression of the symptom than antihistamine.