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Cromakalim Blocks Membrane Phosphoinositide Activated Signals in the Guinea Pig Lung Mast Cells Stimulated with Antigen-Antibody Reactions

Ro, Jai-Youl   (Department of Pharmacology, Yonsei University College of MedicineUU0000936  ); Kim, Ji-Young   (Department of Pharmacology, Yonsei University College of MedicineUU0000936  ); Kim, Kyung-Hwan   (Department of Pharmacology, Yonsei University College of MedicineUU0000936  );
  • 초록

    Cromakalim (BRL 34915), known as an airway smooth muscle relaxant, inhibited the releases of mediators in the antigen-induced mast cell activation. It has been suggested that cromakalim, in part, inhibited mediator releases by inhibiting the initial increase of 1,2-diacylglycerol (DAG) produced by the activation of the other phospholipase system which is different from phosphatidylcholine-phospholipase D pathway. The aim of this study is to further examine the inhibitory mechanism of cromakalim on the mediator release in the mast cell activation. Guinea pig lung mast cells were purified by using enzyme digestion and percoll density gradient. In purified mast cells prelabeled with $[^3H]PIP_2$ , phospholipase C (PLC) activity was assessed by the production of $[^3H]$ insitol phosphates. Protein kinase C (PKC) activity was assessed by measuring the protein phosphorylated from mast cells prelabeled with $[{\gamma}-32P]ATP$ , and Phospholipase $A_2\;(PLA_2)$ activity by measuring the lyso-phosphatidylcholine produced from mast cell prelabeled with 1-palmitoyl-2-arachidonyl $phosphatidyl-[^{14}C]choline$ . Histamine was assayed by fluorometric analyzer, and leukotrienes by radioimmunoassay. The PLC activity was increased by activation of the passively sensitized mast cells. This increased PLC activity was decreased by cromakalim pretreatment. The PKC activity increased by the activation of the passively sensitized mast cells was decreased by calphostin C, staurosporine and cromakalim, respectively. The $PLA_2$ activity was increased in the activated mast cells. The pretreatment of cromakalim did not significantly decrease $PLA_2$ activity. These data show that cromakalim inhibits histamine release by continuously inhibiting signal transduction processes which is mediated via PLC pathway during mast cell activation, but that cromakalim does not affect $PLA_2$ activity related to leukotriene release.


  • 주제어

    Cromakalim .   Mast cell .   Histamine .   Leukotrienes .   Phospholipase C .   Phospholipase $A_2$ .   Protein kinase C.  

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  • 노재열 (11)

    1. 1975 "황금(黃芩)의 심장(心臟)에 대한 약리작용(藥理作用)" 대한약리학잡지 11 (2): 9~17    
    2. 1976 "Caerulein의 흰쥐 취외분비반응에 미치는 phenoxybenzamine의 영향" 대한약리학잡지 12 (2): 7~11    
    3. 1976 "산조인(酸棗仁)의 심장(心臟)에 대한 약리작용(藥理作用)" 대한약리학잡지 12 (2): 13~19    
    4. 1978 "심운동(心運動)에 대한 담즙산의 영향" 대한약리학잡지 14 (1): 41~46    
    5. 1982 "Vitamin A 유도체로 인한 간의 약물대사효소 변동" 대한약리학잡지 18 (1): 65~72    
    6. 1993 "Cromakalim이 해명의 과민반응 매개체 유리에 미치는 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 29 (2): 263~274    
    7. 1994 "인삼 사포닌 단일물질이 알러지 과민반응의 매개체 유리기전에 미치는 영향" The Korean journal of pharmacology : official journal of the Society of Pharmacology, Republic of Korea 30 (2): 243~254    
    8. 1997 "Effects of Ginsenosides on the Mechanism of Histamine Release in the Guinea Pig Lung Mast Cells Activated by Specific Antigen-Antibody Reactions" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (4): 445~456    
    9. 1997 "Helicobacter pylori에 의해 호중구 및 위점막 세포로부터 유도되는 Leukotriene $B_4$의 생성에 미치는 Rebamipide의 영향" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 1 (6): 825~830    
    10. 1998 "The Inhibitory Mechanism of Aloe Glycoprotein (NY945) on the Mediator Release in the Guinea Pig Lung Mast Cell Activated with Antigen-Antibody Complexes" The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 2 (1): 119~131    
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