• The Journal of Korean Physical Therapy
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• 제20권3호
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• pp.53-59
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• 2008

Purpose: The non-receptor-type protein tyrosine kinase Syk (636 amino acids, 72 kDa) is ubiquitously expressed in hematopoietic stem cells and has been widely studied as a regulator and effector of B cell receptor signaling that occurs in processes such as differentiation, proliferation and apoptosis. However, the mechanism relating Syk and p38 mitogen-activated protein kinases (p38MAPK) by endothelin-1 (ET-1, 21 amino acids) stimulation in muscle cells, especially in the volume-dependent hypertensive state, remains unclear. Methods: In this study, we investigated the relationship between Syk and p38MAPK for isometric contraction and enzymatic activity by ET-1 from rat aortic smooth muscle cells and aldosterone-analogue deoxycorticosterone acetate (DOCA) hypertensive state rats (ADHR). Results: The systolic blood pressure was significantly increased in ADHR than in a control group of animals. ET-1 induced isometric contraction and phosphorylation of p38MAPK, which was increased in muscle strips from ADHR. Increased vasoconstriction and phosphorylation of p38MAPK induced by treatment with 30 nM ET-1 were inhibited by the use of 10${\mu}M$ SB203580, an inhibitor of p38MAPK from ADHR. Furthermore, ET-1 induced isometric contraction and phosphorylation of Syk and p38MAPK, which were increased in the aortic smooth muscle cells. Increased tension and phosphorylation of Syk and p38MAPK induced by ET-1 were inhibited by SB203580 from rat aortic smooth muscle cells. Conclusion: These results, suggest that the Syk activity affects ET-1-induced contraction through p38MAPK in smooth muscle cells and that the same pathway directly or indirectly is associated with volume dependent hypertension. The findings suggest the need to develop cardiovascular disease-specialized physical therapy.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.343-347
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• 2006

The present study was designed to investigate the effects renin-angiotensin-aldosterone system (RAAS), endothelin (ET) and local natriuretic peptide (NP) system for glomerulopathy induced in the experimental bilateral ureteral obstructive rats. Sprague-Dawley male rats ($200{\sim}220g$ body weight) were bilaterally obstructed by ligation of the proximal ureters for 24 hours. Control rats were treated in the same ways, except that no ligature was made. The glomeruli were isolated from cortex by graded sieve methods, and the mRNA expressions of local renin-angiotensin system (RAS), aldosterone synthase (CYP11B2), endothelin-1 (ET-1) and NP system were determined by real-time polymerase chain reaction. Following the bilateral ureteral obstruction, the mRNA expressions of renin, angiotensin converting enzyme 1 as well as ET-1 were increased, while that of angiotensin converting enzyme 2 was not changed. The expressions of CYP11B2 and angiotensin II receptors were not changed. C-type natriuretic peptide (CNP) expression was increased, while its receptors (natriuretic peptide receptor-B) were not changed. We suggest that the upregulation of local RAS and ET playa role in the progressive glomerular injury, and that the enhanced CNP activity also plays a compensatory role in obstructive uropathy in the glomerulus.

• 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.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권5호
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• pp.565-572
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• 1997

In the freshly isolated rat nephron, the effect of endothelin-1, -2 and -3 (ET-1, -2 and -3) on cytosolic free calcium concentration ($[Ca^{2+}]_i$) was determined using the fluorescent indicator Fura-2/AM. $[Ca^{2+}]_i$ increase was investigated in 9 parts of the single nephron including glomerulus (Glm), $S_1,\;S_2,\;S_3$, cortical and medullary thick ascending limb and cortical (CCT) and outer medullary collecting tubule (OMCT). Endothelins increased $[Ca^{2+}]_i$ in Glm (ET-1; $127{\pm}17%$, ET-2; $93{\pm}5%$, ET-3; $169{\pm}17%$), CCT (ET-1; $30{\pm}6%$, ET-2; $38{\pm}19%$, ET-3; $158{\pm}18%$) and OMCT (ET-1; $197{\pm}11%$, ET-2; $195{\pm}11%$, ET-3; $215{\pm}37%$) at 10-7 M. In OMCT, ET-1 and ET-2 increased $[Ca^{2+}]_i$ in a dose-dependent manner ($10^{-10}{\sim}10^{-6}$ M). To the contrary, ET-3-induced $[Ca^{2+}]_i$ rise was begun from $10^{-12}$ M. BQ-123Na, an antagonist of ETA receptor, at $10^{-4}$ M inhibited about 30% of $[Ca^{2+}]_i$ rise induced by ET-1 and -3. Binding experiments using $[^{125}I]ET-3$ showed the existence of $ET_B$ receptor in OMCT. This binding was replaced by ET-1, ET-2 or ET-3 by the almost same degree but not by angiotensin II or vasopressin.

• Tuberculosis and Respiratory Diseases
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• 제50권3호
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• pp.300-309
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• 2001

배 경 : 패혈증의 병태생리에는 많은 인자들이 관여를 한다. 이중 ET-1은 혈관수축 및 다장기 부전 등을 초래하고 IL-8은 호중구 매개성 염증반응을 유도하는 역할을 하며, 임상적 지표로서도 유용성이 알려지고 있다. 본 연구는 패혈증 환자에서 ET-1과 IL-8의 혈중농도를 연속적으로 측정하여 변화 양상과 상호 관련성을 평가하고 임상적인 의의를 조사하고자 한다. 방 법 : 패혈증 환자 19예에서 1일, 3일, 7일, 14일에 연속적으로 채혈을 하였고 APACHE III 점수를 측정하였다. 혈청 검체에서 ET-1과 IL-8의 농도를 immunoassay 법으로 측정하였다. 결 과 : 패혈증 환자에서 정상 대조군에 비하여 혈청 ET-1이 유의하게 높았다. 패혈증 환자에 있어서 1일 및 7일 ET-1은 생존군보다 사망군에서 더 높았다. 패혈성 쇼크를 동반한 군에서 1일 ET-1이 높았으며, 혈청 ET-1은 혈청 creatinine과 1일, 7일, 14일에 유의한 상관성이 있었다. 혈청 ET-1과 IL-8 농도는 14일에 서로 유의한 상관성이 나타났다. 결 론 : 패혈증에 있어서 혈청 ET-1은 예후, 패혈성 쇼크, 신부전 등과 관련성이 있었고 IL-8과도 상관성을 보여 임상적인 평가 및 예후 인자로서 유의성을 보였다.

• Clinical and Experimental Reproductive Medicine
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• 제31권4호
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• pp.235-244
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• 2004

Objective: The effects on spermatogenesis by expression of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were investigated. Materials and Methods: Testicular specimens were obtained from 40 infertile males due to primary testicular failure and from 10 fertile males with other urologic problems. The specimens of infertile males were devided into 4 groups according to histologic findings; Sertoli cell only syndrome (A), maturation arrest (B), hypospermatogenesis (C) and sloughing and disorganization (D). VEGF and ET-1 expression were detected with immunohistochemical stain. Results: VEGF expression on Leydig cell was detected in all cases. But, VEGF expression rates on germ cell were significantly higher in infertile group B, C, D compared to that of the control group (p<0.05). ET-1 expression rates on Leydig cell was significantly lower in all infertile group compared to that of the control group (p<0.05). But, ET-1 expression rates on Sertoli cell was significantly higher in all infertile group compared to that of the control group (p>0.05). In germ cell of infertile group, LH, FSH and prolactin were significantly decreased, and estradiol is increased in positive stain group on ET-1 immunohistochemical stain (p<0.05). VEGF and ET-1 expression were not correlated mean seminiferous tubule diameter (p>0.05). Conclusions: Abnormal spermatogenesis would be reflected in VEGF expression in germ cell.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.193-193
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• 1996

Endothelin-1, which is a peptide originally isolated from cultured porcine aortic cell, has been found to play a crucial role in potentiating the vasoconstriction mitogenesis, and chemotaxis. In the present study, we examined the level of endothelin-1 in the brain, spinal cord and blood from rat with experimental allergic encephalomyelitis(EAE). At the peak stage of EAE(grade 3), endothelin-1 level in the spinal cord of rat with EAE increased two folds as compared with that of sham-treated rats, and subsequently decreased to the level of control at the recovery stage. In the endothelin-1 immunocytochemistry, endothelin-1 immunopositive cells and ED-1, macrophage marker immunopositive cells observed in the spinal cord of peak stage(grade 3). These Findings suggest that endothelin-1 play the important role in progression of EAE.

• Animal cells and systems
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• 제4권1호
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• pp.63-70
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• 2000

The distribution of receptor subtypes for endothelin (ET) in the kidney of the freshwater turtle, Amyda japonica, was examined by quantitative in vitro receptor autoradiography using iodinatd mammalian type ET-1 ($^125$/I-ET-1)as a radiolabeled ligand. Specific $^125$/I-ET-1 bindings were localized to renal tubules, renal arteries and ureter with binding densities of 111.21 $\pm$ 19.14, 182.13$\pm$10.57 and 219.46$\pm$12.83 amol/$mm^2$. respectively. Binding dissociation constants in renal tubules, renal arteries and ureter were 1.05 $\pm$ 0.63, 2.03 $\pm$0.56 and 1.70$\pm$0.47nM, respectively. Receptor subtypes for ET in the kidney were characterized by competition with BQ 123 and BQ 788 as specific antagonists for ET receptors, type A (ET$_A$ ), and type B (ET$_B$) subtypes, respectively. Specific $^125$/I-ET-1 bindings in renal arteries and ureter were potently inhibited by BQ 123 in a dose-dependent manner, whereas BQ 788 was not in competing for specific $^125$/I-ET-1 bindings in this structure. However, specific $^125$/I-ET-1 bindings in renal tubules were inhibited more potently by BQ 788. Therefore, these results indicate that specific ET receptors are localized in renal tubules, renal arteries and the ureter of the freshwater turtle. Results also suggest that the predominant ET receptor subtypes are like the ETA receptor in renal arteries and ureter, and like the ET/$_A$ receptor in the renal tubule.