• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.191-191
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• 1996

BQ-123, a selective $ET_{A}$ receptor antagonist, reverses various responses induced by Endothelin-1 and it has been reported that BQ-123 ameliorates the cerebrovascular constriction, hypertension, and decrease of blood flow. Previously, we announced that the level of Endothelin-2 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of $ET_{A}$ receptor antagonist, BQ-123(10nmol) was done for visualizing the role of endothelin-1 on the pathogenesis of EAE. BQ-123 apparently blocked the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model following BQ-123, suggests that BQ-123 is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.192-192
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• 1996

Endothelin has $ET_{A}$ type and $ET_{B}$ type receptors, and it has been thought that ET-1 proves vasoconstriction effect via $ET_{A}$ receptor and vasodilation via $ET_{B}$ receptor. Recently, it has been reported that $ET_{B}$ receptor is also related to the vaso-constriction. Bosentan is a $ET_{A+B}$ receptor antagonist, and proves it's effect on trauma and ischemia. We already announced that the level of Endothelin-1 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of Bosentan, $ET_{A+B}$ receptor antagonist, (300nmol/body) was done for observing the role of endothelin-1 on the pathogenesis of EAE. Bosentan ameliorated the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model suggests that Bosentan is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• 대한화장품학회지
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• 제24권3호
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• pp.134-145
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• 1998

Facial hyperpigmentation in women, which is considered to be a serious cosmetic disability and a cause of mental distress, requires proper management. Melanocyte dendricity is a crucial factor affecting epidermal pigmentation. We found that BQ-788, the endothelin-B (ETB) receptor antagonist, blocks the formation of multi-dendricity which is induced by cocultured keratinocytes. Melanocytes in vivo show numerous dendrites which are in close contact with multiple keratinocytes, forming the epidermal-melanin unit. While melanocytes transfer their melanosomes into the neighboring keratinocytes via dendrites, keratinocytes secrete many growth factors and cytokines that influence viability, morphology, and melanin formation of melanocytes. Endothelin-1 (ET-1), prostaglandin E2(PGE2), and leukotriene-C4 (LT-C4) have been suggested as the candidates for increasing dendricity. Other reports suggested that ET-1 has stimulatory effects on proliferation and melanin formation of melanocytes in vitro. In the present study, using type-specific ET receptor antagonists, we observed how the morphology of melanocytes could be modulated in a coculture system. In addition, the roles of ET-1 for morphology and proliferation on melanocytes were evaluated in different culture media. We suggest that ET-1 increases dendricity and proliferation of melanocytes, and that its dendrite-inducing effect and mitogenic effect are regulated independently.

• Asian-Australasian Journal of Animal Sciences
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• 제20권10호
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• pp.1503-1509
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• 2007

Endothelin-1 (ET-1) is an important factor in regulation of cardiovascular tone in humans and mammals, but the biological function of ET-1 in the avian vascular system has not been determined. The purpose of this study was to characterize the role of endogenous ET-1 in the vascular system of poultry by investigating the effect of endothelin A receptor ($ET_AR$) antagonist BQ123 on the femoral artery pressure (FAP) and the pulmonary artery pressure (PAP) in broiler chickens. First, we found that plasma and lung homogenate ET-1 levels were both increased with age over the seven weeks life cyccle of broiler chickens. Second, 60 min after intravenous injection, BQ123 ($0.4{\mu}g\;kg^{-1}$ and $2.0{\mu}g\;kg^{-1}$, respectively) induced a significant reduction in FAP and PAP (p<0.05). Third, chronic infusion of BQ123 ($2.0{\mu}g\;kg^{-1}$ each time, two times a day) into abdominal cavities led to significant decrease in systolic pressure of the femoral (p<0.05) and pulmonary arteries (p<0.01) in broiler chickens at 7 and 14 days after treatment. Taken together, the $ET_AR$ antagonist BQ123 lead to a significant reduction of FAP and PAP, which suggests that endogenous ET-1 may be involved in the maintenance and regulation of systemic and pulmonary pressure in broiler chickens.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.119-123
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• 2001

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.92-92
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• 1997

Stereotaxic apparatus를 이용하여 흰쥐의 두개골을 천공하여 periaqueductal gray matter에 정확히 cannula를 삽입하여 1일 이상의 방치후 여기로 약물을 투여하여 일군의 동물들은 행동의 변화를 관찰하고, 일군의 동물들은 경동맥에서의 혈압과 심박수의 변화를 관찰한다. 결과: ET-1에 의해 유발된 barrel-rolling은 NMDA receptor-selective antagonist인 MK-801에 의해 유의성있게 억제되었으며, NOS antagonist인 L-NAME과 NO scavenger인 Hemoglobin에 의해서도 유의성 있게 억제되었다.

• Tuberculosis and Respiratory Diseases
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• 제48권2호
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• pp.210-222
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• 2000

한국산 잡견 11마리를 대상으로 자가 혈병을 이용한 급성 폐색전증을 만들고 ET 수용체 길항제를 투여하여 다음과 같은 결과를 얻었다. 1. 혈병 투여후 폐동맥압은 상승하였고 심박출량은 감소하였으며 페혈관 저항은 증가하였다. 동맥혈 산소분압과 혼합 정맥혈의 산소 분압이 감소하였고 사강호흡이 증가하였고 생리적 단락이 증가하였으나 전신혈압은 변동이 없었다. 모든 측정치는 수용체 길항제 투여군과 대조군간에 차이를 보이지 않았다. 2. ET-1 수용체 길항제 투여후 전신혈압, 동맥 및 혼합정맥혈산소 분압, 동정맥 단락, 및 사강호흡의 정도는 두군간에 차이를 보이지 않았으나, 폐동맥압, 심박출량, 폐혈관 저항은 길항제 투여 30분후부터 수용체 길항제 투여군과 대조군간에 차이를 보이기 시작하여 210분후까지 지속되었다. 3. ET-1의 농도는 색전전(Baseline)에 비하여 색전후 동맥혈, 혼합정맥혈, 및 그 비(동맥혈/혼합정맥혈)가 증가를 보였고, 수용체 길항제 투여후 투여군에서는 대조군에 비해 ET-1의 농도 증가가 의미 있게 높았다. 4. 면역조직화학염색상에서 폐색전증이 유발된 개의 폐혈관 및 폐조직에서 색전을 투여하지 않은 정상 개의 조직에 비해 ET-1의 발현이 증가되었다. 5. Northern blot 상에서 폐색전이 일어난 폐조직의 preproET-1 mRNA 발현은 색전이 일어나지 않은 개의 폐조직에 비하여 증가되었다.

• Clinical and Experimental Pediatrics
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• 제52권6호
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• pp.689-695
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• 2009

목 적 : 폐동맥 고혈압은 지속적인 폐혈관 저항의 증가로 우심실 부전에 이르게 되는 질병 상태를 일컫는다. 폐동맥 고혈압의 기전으로 폐혈관의 내피세포로부터 endothelin 분비가 증가되어 세포 증식 촉진, 세포 자멸 억제, 혈관 수축, 염증 반응을 통해 폐혈관의 재형성에 관여함이 제시되었다. Bosentan은 endothelin 수용체에 결합하여 효과를 차단시키는 약물로 개발되었다. 이에 monocrotaline으로 폐고혈압을 유발시킨 동물에서 non-selective endothelin receptor blocker인 bosentan을 투여하였을 때 폐동맥 고혈압 발생에 미치는 효과를 알아보고자 본 연구를 시행하였다. 방 법 : 체중 250 g 내외의 4주령 가량 된 자성 Sprague-Dawley 백서를 대조군, monocrotaline군, bosentan군으로 나누었다. Monocrotaline군과 bosentan군에는 monocrotaline 수용액 60 mg/kg를 배부에 1회 피하 주사하고 대조군에는 동량의 생리식염수를 주사하였다. Bosentan군에는 bosentan ($20mg{\cdot}kg^{-1}{\cdot}day^{-1}$)을 monocrotaline 투여 직후부터 매일 1일 2회 위관 영양법으로 투여하였다. 7일, 14일, 28일에 각각 동물을 희생시켜 심장의 무게를 우심실벽, 좌심실벽, 심실간벽으로 나누어 기관의 무게를 측정하고 조직 검사를 위해 양측 폐를 포르말린 수용액에 고정하였다. 결 과 : 7일, 14일, 28일째 평균 체중은 대조군에 비해 monocrotaline군과 bosentan군이 유의하게 적었다. 우심실/(좌심실＋심실간벽)의 무게 비율은 28일째 monocrotaline군($0.71{\pm}0.10mg/g$)에 비해 bosentan군($0.49{\pm}0.09mg/g$)이 유의하게 적었다(P<0.05). 폐세동맥의 조직형태학적 분석 결과 실험 28일째 monocrotaline투여에 의해 유발된 중막 비후 소견이 bosentan 투여에 의해 현저하게 저하된 것으로 나타났다(monocrotaline군 $49.94{\pm}10.06$ vs bosentan군 $47.09{\pm}10.48$, P<0.05). 또한 호흡성 세기관지 이하의 폐포에 분포하는 근육성 폐세동맥의 숫자도 monocrotaline 투여에 의해 증가되었으나 14, 28일째 bosentan군에서는 현저하게 적은 것으로 나타났다. 결 론 : Monocrotaline으로 유도한 백서의 폐고혈압에서 bosentan을 투여하고 초기 경과를 관찰한 결과, 2주째부터 우심실 비대가 억제되었고 4주 이내 사망률도 낮아 endothelin receptor에 대한 길항 작용의 효과로 해석될 수 있겠다.

• Tuberculosis and Respiratory Diseases
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• 제67권4호
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• pp.275-280
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• 2009

Interstitial lung disease (ILD) is a group of diseases characterized by pulmonary interstitial inflammation. Finally the inflammation results in pulmonary fibrosis and impairment of oxygen transportation. The causes of idiopathic interstitial pneumonia (IIP) are unknown. Diagnosis of IIP is not easy, especially distinguising between nonspecific interstitial pneumonia and usual interstitial pneumonia (UIP). First line treatments of IIP include corticosteroids and immune modulators, which have limited effect. Currently, several drugs are being researched to prevent and treat fibrosis. Newer drugs that may useful to treat pulmonary fibrosis include endothelin receptor antagonist, recombinant soluble TNF receptor antagonist, and cotrimoxazole. The causes of IIP are largely unknown, treatment is not specific, and prognosis is poor. Recent studies are underway to investigate the pathogenesis and treatment of IIP and pulmonary fibrosis. As the pathogenesis of IIP is elucidated, better treatments will emerge.

• The Korean Journal of Physiology and Pharmacology
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• 제18권3호
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• pp.201-209
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• 2014

The present study was designed to investigate the efficacy of selective $ET_A$ receptor antagonist, ambrisentan on hyperhomocysteinemia-induced experimental vascular dementia. L-methionine was administered for 8 weeks to induce hyperhomocysteinemia and associated vascular dementia in male rats. Ambrisentan was administered to L-methionine-treated effect rats for 4 weeks (starting from $5^{th}$ to $8^{th}$ week of L-methionine treatment). On $52^{nd}$ day onward, the animals were exposed to the Morris water maze (MWM) for testing their learning and memory abilities. Vascular endothelial function, serum nitrite/nitrate levels, brain thiobarbituric acid reactive species (TBARS), brain reduced glutathione (GSH) levels, and brain acetylcholinesterase (AChE) activity were also measured. L-methionine-treated animals showed significant learning and memory impairment, endothelial dysfunction, decrease in/serum nitrite/nitrate and brain GSH levels along with an increase in brain TBARS levels and AChE activity. Ambrisentan significantly improved hyperhomocysteinemia-induced impairment of learning, memory, endothelial dysfunction, and changes in various biochemical parameters. These effects were comparable to that of donepezil serving as positive control. It is concluded that ambrisentan, a selective $ET_A$ receptor antagonist may be considered as a potential pharmacological agent for the management of hyperhomocysteinemia-induced vascular dementia.