The effects of removal of epithelium on mediator release from the isolated guinae - pig trachea sensitized by IgG1 & IgE antibodies

노재열,김경환,( C . K . Buckner,F . M . Graziano ) 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 1990 추계학술대회 초록집 Vol.1990 No.-

인삼 사포닌 단일물질이 알러지 과민반응의 매개체 유리기전에 미치는 영향

노재열,김경환,Ro, Jai-Youl,Kim, Kyung-Hwan 대한약리학회 1994 대한약리학잡지 Vol.30 No.2

Inflammatory diseases, allergic and asthmatic disorders are caused by the mediator release from the activation of the phospholipase C (PLC), phospholipase D (PLD), methyltransferase or adenylate cyclase etc. during IgG or IgE cross-linking of high affinity receptors on mast cells or basophil surface. One important enzyme activated after IgG or IgE receptor cross-linking is PLD, the enzyme which converts phosphatidylcholine (PC) to phosphatidic acid (PA). Under the hypothesis that these may be some differences in mediator release according to the difference in PLD activity, we attempted to confirm the ginseng saponin effects on the PLD activity. We examined the PLD activity during the passively sensitized mast cell activation in the presence of single component of ginsenosides $(Rc,\;Rg_1,\;Rg_2,\;Rg_3)$. We also measured the amount of mediators (histamine and leukotrienes) released by stimulating with ovalbumin (OA) or calcium ionophore (CaI), Guinea Pig lung mast cells were purified using enzyme digestion, count current elutriation, and discontinuous Percoll density gradient. In purified mast cells prelabeled with $[^3H]$ arachidonic acid or $[^3H]$ palmitic acid, PLD activity was assessed more directly by the production of labeled PEt by PLD-mediated transphosphatidylation in the presence of ethanol. Histanine release was determined by Spectrophotofluorometry, and leukotrienes by radioimmunoassay. The PLD activity during the passively sensitized mast cell activation is increased up to $3{\sim}5times$. The PLD activity during the passively sensitized mast cell activation in the presence of all ginsenosides is decreased up to $4{\sim}11$ times. $Rg_l\;and\;Rg_2$ ginsenoside pretreatment decreased histamine and leukotrienes by 50% in the OA-induced or by 40% in the Cal-induced mast cell after passively sensitization. Rc pretreatment poorly decreased histamine but leukotrienes decreased by 70% in the OA-induced or by 35% in the Cal-induced mast cell. $Rg_3$ ginsenoside pretreatment increased histamine release without challenging OA or Cal but leukotrienes decreased. These observations indicate that single unit of ginsenosldes may be an important contributor to inhibit the release of histamine and leukotrienes in the guinea pig lung mast cells, that inhibits the PLD-mediated formation of DAG evoked by mast cell activation.

알레르기에서 신호전달과 약물작용

노재열 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 1993 춘계학술대회 초록집 Vol.1993 No.-

마우스, 랫트, 해명에서 집먼지 진드기 추출물의 일반 약리시험과 급성 및 아급성 독성에 관한 연구

노재열,김경환 한국독성학회 1998 Toxicological Research Vol.14 No.2

It has been reported that 50~70% of child asthma, bronchial asthma in adult, and allergic rhinitis are caused by house dust mite. The antigen extracted from house dust mite has been used for effective treatment against allergic diseases and for clinical test. This house dust mite antigen has been entirely imported from abroad. However, the composition and content of all the antigen imported vary from a brand to other brand. Thus, we need to standardize the composition and content of the antigen by developing it domestically. We proceeded pre-clinically general pharmacological test and toxicological test that are required for the eventual human use by utilizing the house dust mite cultured in Korea. In order to obtain information on general pharmacological tests such as its toxic signs in tissues or organs which are mainly affected, we examined the effect of house dust mite on the tensions of the isolated tissues and heart rates of cardiac muscle by recording with force displacement transducer of polygragh (Glass Model 7). We determined lethality of antigen extracted from house dust mite in mice and guinea pigs. We examined acute and subacute toxicity by administrating house dust mite extract of 500, 100, 20 times of the expected clinical dose. In male and female mice and guinea pigs, given a sigle intraperitoneal dose of antigen, $LD_{50}$ values were over 5.0 $\textrm{m}{\ell}$/kg, respectively. In animals administrated with house dust mite, there were no significant change of clinical symptom, body weight, food consumption, water consumption, eye examinations, urinalysis, blood biochemistry, and histopathological examinations in any animals tested. We found no toxic effect of this house dust mite. These results show that the house dust mite cultured by us could be used in the development of medicine against allergic diseases caused by the antigen of house dust mite.

비반세포의 신호 변환 경로와 관련된 항 알레르기 및 천식 약제들

노재열 대한천식알레르기학회 2000 천식 및 알레르기 Vol.20 No.4

N/A

약물치료의 이론

노재열 대한소아알레르기호흡기학회 1994 Supplement Vol.4 No.2

N/A

일반연제 ( A ) : 9 . Aloe 당단백의 비반세포 활성화시 매개체 유리 억제 기전

노재열,김지영,이병철,박영인 대한천식 및 알레르기학회 ( 구 대한알레르기학회 ) 1998 춘계학술대회 초록집 Vol.1998 No.-

염증세포의 신호전달

노재열 대한천식알레르기학회 1995 천식 및 알레르기 Vol.15 No.2

심운동(心運動)에 대한 담즙산의 영향

노재열,김혜영,홍사석,Ro, J.Y.,Kim, H.Y.,Hong, S.S. 대한약리학회 1978 대한약리학잡지 Vol.14 No.1

The effects of sodium taurocholate(STC) and sodium deoxycholate(SDC) on cardiac function were examined by using isolated atria of rabbit and guinea pig and heart of anesthetized frog. Also the antiarrythmic action of STC and SDC on atrial arrhythmias induced by epinephrine or ouabain was studied. The results were following. The cholates exhibited a slight decrease in rate and contractile amplitude of the isolated rabbit atria. The cholates abolished partially the spontaneous arrhythmic occurring in isolated rabbit and guinea pig atria but no effect on the atrial arrhythmia induced by ouabain and epinephrine was observed. Concomitant administration of cholates with ouabain produced a marked prolongation of atrial arrhythmia in comparison to that of ouabain alone in both isolated rabbit and guinea pig atria. The cholates exhibited a marked prolongation in ventricular arrhythmia and cardiac arrest time in comparison to that of ouabain treatment. However, the combined treatment with cholates and ouabain produced a slight prolongation in comparison to that of ouabain alone in the heart of anesthetized frog. The above results suggest that cholates have a slight antiarrythmic effect on the heart but this effectiveness is different from those of propranolol that is non-selective antiarrhythmic drug.

Effects of Crormakalim on the Release of Mediators in Hypersensitivity of Guinea pig

노재열,김경환,Ro, Jai-Youl,Kim, Kyung-Hwan The Korean Society of Pharmacology 1993 대한약리학잡지 Vol.29 No.2

Potassium $(K^+)$ channels are present in airway smooth muscle cells, and their activation results in hyperpolarization and relaxation. Because these effects may have therapeutic relevance to hypersensitivity and asthma, we examined the effect of a potassium channel activator, cromakalim (BRL 34915, CK) on the release of mediators from superfused tracheal and parenchymal strips after passive sensitization with $IgG_1$ antibody. Both tissues were superfused with CK $(2{\times}10^{-6}\;M)$ for 30 min and challenged with CK and antigen (Ox-HSA). Using monodispersed, partially purified, highly purified guinea pig lung mast cells, we also examined the effect of CK on mediator release from these cells after passive sensitization with $IgG_{1}$ antibody $({\alpha}-OA)$. Guinea pig lung mast cells were purified using enzyme digestion method, count current elutriation, and discontinuous Percoll density gradient. After CK pretreatment, passively sensitized mast cells were challenged with varying concentration of antigen (OA, immunological stimuli) or with varying concentration of calcium ionophore (CaI, non-immunological stimuli). Histamine (Hist) release was determined by spectrophotofluorometry, and leukotrienes (LT) by radioimmunoassy. CK pretreatment decreased Hist by 35% and LT release by 40% in the antigen-induced tracheal tissue after $IgG_1$ sensitization but did not decrease the contractile response. In the antigen-induced parenchymal tissue CK decreased Hist release by 25% but poorly decreased LT. Both immunologic and non-immunologic stimuli caused a dose-dependent release of Hist and LT from monodispersed, partially purified and highly purified lung mast cells. Verification of LT release was obtained by the use of 5-lipoxygenase inhibitor, A64077 (Zileuton). CK decreased Hist and LT release by 20% respectively in the OA-induced guinea pig lung mast cells after $IgG_1$ sensitization. The inhibitory effects of CK on the Hist and LT release in the Ox-HSA-induced airway smooth muscle tissues or in the OA-induced and CaI-induced mast cells after $IgG_1$ sensitization were completely blocked by TEA and GBC. These studies show that guinea pig lung mast cells seem to be an important contributor to LT release, and that CK (which has been known as an airway smooth muscle relaxant) can in part act to inhibit mediator release in the antigen-induced airway smooth muscle, and that CK may also act to inhibit mediator release in the OA-induced and CaI-induced highly purified mast cells. These results suggest that Hist and LT release evoked by mast cell activation might in part be associated with $K{^+}4 channel activity. $K^+$통로는 기도 평활근 세포에 존재하며 이들 통로가 활성화되면 평활근의 과분극의 결과 이완작용이 나타난다. $K^+$통로의 이런 효과는 과민반응과 천식 치료에 응용될 수 있으므로 우리는 $K^+$통로 개방제인 cromakalim (BRL34915, CK)이 $IgG_1$ 항체로 감작시킨 기도 및 폐조직으로 부터 유리되는 매개체 유리에 미치는 영향을 조사하였다. 피동적으로 감작된 두 조직은 $2{\times}10^{-6}\;M$의 CK로 30분동안 superfusion시킨 후 CK와 항원 (Ox-HSA) 0.1 mg/ml로 자극하였다. 또한 비만세포를 이용하여 CK의 효과를 조사하였다. 해명 폐조직 비만세포는 효소에 의한 digestion method (monodispersed; 미분리 정제), count current elutriation에 의한 방법(partially purified; 부분분리정제), 그리고 discontinuous Percoll방법(highly purified; 순수분리정제)에 의해 순수 분리되었다. CK로 전처치한후, 피동적으로 감작된 비만세포는 OA와 CaI의 여러 농도에 의해 자극되었다. 유리된 Hist은 spectrophotofluorometry에 의해, LT는 면역방사법에 의해 측정되었다. CK 전처치는 $IgG_1$ 감작후 항원에 의해 자극된 기도 조직에서 Hist 유리량을 35%까지, LT 유리량은 40%까지 감소시켰으나 기도 평활근 수축력에는 반응을 나타내지 못하였다. 항원 유도 폐조직에 있어서 CK전처치는 Hist유리량을 25%까지 감소시켰으나 LT 유리에는 미약한 감소를 나타내었다. 해명의 미분리정제, 부분분리정제, 그리고 순수 분리 정제된 비만세포로부터 Hist과 LT은 면역자극(OA)이나 비면역자극(CaI)에 의해 농도 의존적으로 유리되었다. 비만세포에서 유리된 LT는 5-lipoxygenase억제제인 A64077에 의해서 억제됨이 확인되었다. CK전처치는 OA유도 및 CaI유도 해명 폐조직 비만세포에서 Hist과 LT 유리량을 20%까지 감소시켰다. $IgG_1$ 감작후 Ox-HSA유도 기도 평활근 조직이나 혹은 OA유도 및 CaI유도 비만세포에서 Hist과 LT유리에 미치는 CK의 억제효과는 TEA와 GBC에 의해 완전히 봉쇄되었다. 이상의 결과에서 폐조직 비만세포는 LT를 유리할 수 있는 세포로 간주되며, 기도 평활근 이완제로 알려져 있는 CK은 특수 항원 유도 기도 평활근조직에서 매개체 유리를 부분적으로 억제하며, CK은 또한 OA유도 및 CaI로 유도된 순수분리 정제된 비만세포에서 매개체 유리를 부분적으로 억제하는 것으로 보아 비만세포가 활성화시 야기되는 여러 생화학적 현상중에서 미약하나마 $K{^+}$통로가 관여할 것으로 사료된다.