• 대한물리치료과학회지
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• 제13권2호
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• pp.99-119
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• 2006

Endothelin (ET) is a 21 amino acid peptide with multifunctional effects on the vasculature as well as a variety of other cell types such as respiratory, gastrointestinal, urogenital, endocrine, central nervous systems, and others. Endothelin has emerged as a modulator by autocrine and paracrine actions for many cellular activities, including vasoconstriction, cell proliferation, hormone production, neurotransmitter and/or neuromodulator. The endothelin family consists of three closely related peptides, ET-1, ET-2, and ET-3 derived from separate genes, such as chromosome 6, 1, and 20, respectively. ET-1 is the predominant isoform produced in the cardiovascular system and about which most is known. Endothelin receptors are seven-transmembrane GTP-binding protein-coupled receptors, which are classified into endothelin-A (ETA) and endothelin-B (ETB) receptors. Interestingly, recent evidence is accumulating to suggest that ET -1 may contribute to a variety of pain states such as allodynia and hyperalgesia in animals and humans. Therefore, in this review the biological characteristics and contraction-related mechanism of endothelin-1 in mammalian cells will be summarized. Especially, we focus on multifunctional roles for ET-1 in noxious stimulation-induced pain for the study of pain specialized physical therapy.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.149-153
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• 2008

Endothelin-1 (ET-1) is unequivocally elevated in the kidney with ischemic acute renal failure (ARF), whereas ET receptors ($ET_AR$ and $ET_BR$) are variably expressed. Although renal functional and structural changes are similar between ischemic and nephrotoxic ARF, there are few reports on the alteration in the ET system in nephrotoxic ARF. This study was, therefore, undertaken to investigate changes in renal expression of ET-l and its receptors in nephrotoxic ARF induced by cisplatin. Mice were intraperitoneally injected with 16 mg of cisplatin/kg at a single dose, and the expression of mRNA and protein was then quantified by real-time RT-PCR and Western blot, respectively. Immunohistochemistry was conducted for localization. Three days after treatment, ET-1 transcript in cisplatin-treated mice was thirteen times higher than that in controls, whereas ET-1 peptide was increased by 1.5-fold. Cisplatin caused a 2-fold increase in the levels of ETAR mRNA and protein. Most of the increased immunoreactive ET-1 and ETAR were localized in damaged tubules. Neither the expression of ETBR mRNA nor the abundance and immunoreactive level of ETBR protein were changed. The findings suggest that the individual components of the renal ET system are differentially regulated in cisplatin-induced nephrotoxic ARF.

• The Korean Journal of Pain
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• 제11권1호
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• pp.36-40
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• 1998

Background: Recently, it has been demonstrated that endothelin(ET) and endothelin related peptides are present in the blood and plasma ET levels are increased after operation. But the causes of increasing plasma ET levels are not clearly understood. This current study was to investigate the relationship between postoperative pain and endothelin. Methods: Thirty adult patients, scheduled for upper abdominal operation under general anesthesia, were included. After operation, epidural catheterization was done for postoperative analgesia. Before induction, on complained of pain and 1 hour after analgesics administration, blood samples were obtained to measure plasma ET levels. Plasma ET concentration was determined by radioimmunoassay. Pain score was measured by visual analogue score(VAS). Mean arterial pressure(MAP) and heart rate(HR) were also recorded every sampling time. Results: There were no significant changes in plasma ET levels at the time before induction versus at the time of the pain complaints and at 1 hour after analgesic administration. Pain score was significantly reduced after epidural analgesia. There was no significant correlations between pain score and plasma ET levels. There were no significant correlation between plasma ET levels and either MAP or HR. Conclusions: These results indicate that there is lack of relationship between postoperative pain and endothelin.

• Tuberculosis and Respiratory Diseases
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• 제44권5호
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• pp.1114-1124
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• 1997

연구배경 : Endothelin(이하 ET로 약함)은 폐혈관 내피세포에서 생산되며 강한 혈관 수축작용이 있는 peptide이다. 일차성 폐동맥고혈압과 급성 폐동맥색전증 환자의 혈장내 ET이 증가하고 이들 질환에서의 심폐기능장애에 ET이 중요한 역할을 하리라고 추측되나 ET증가의 기전에 대해서는 알려진 바 없다. 이들 두 질환은 모두 혈전증이 중요한 병태생리 소견이므로 저자들은 혈소판과 활성화된 혈소판에서 유리된 매개체들이 폐혈관 내피세포에서 ET 생산을 증가시킬 것이라고 가정하고 이를 확인하기 위하여 연구를 시행하였다. 방 법 : 소 폐동맥내피세포 배양배지에 혈소판, thrombin(0.1~10u/ml), transforming growth factor-${\beta}1$(TGF-${\beta}1$, 1-1000pM), serotonin(1-100uM), 및 내독소(1ug/ml)를 첨가한 후 18시간 배양하여 배지내로 유리된 immunoreactive ET(이하 ir-ET로 약함)을 방사선면역측정법으로 정량분석 하였다. 결과 : 소 폐동맥내피세포 배양 상청액내 ir-ET은 배양 시간에 비례하여 증가하였으며 혈소판 $10^8/ml$을 첨가한 군에서는 배양 8시간 및 18시간 후에 대조배지군에 비해 유의하게 높았다(p<0.05). 혈소판 첨가군에서 배양 상청액내 ir-ET은 혈소판의 수가 증가함에 따라 증가하는 경향을 보였고 $10^8/ml$에서는 대조배지군에 비해 유의하게 높았다 (0<0.05). Ir-ET를 증가시키지 않는 혈소판 ($10^7/ml$)에 ir-ET을 유의하게 증가시키지 않는 농도의 thrombin (0.1u/ml) 또는 내독소(1ug/ml)를 각각 첨가한 군에서 배양 상청액내 ir-ET은 배지 대조군과 단독 첨가군 (thrombin 0.1u/ml, 내독소 1ug/ml)에 비해 각각 유의하게 높았다(p<0.05). 소 폐동맥내피세포 배양 상청액내 ir-ET은 thrombin(1-10ug/ml), TGF-${\beta}1$(100-1000pM) 첨가군에서 각각 대조배지군에 비해 유의하게 높았으며 (p<0.05), serotonin(1-100uM) 첨가군은 대조배지군파 유의한 차이가 없었다. 결 론 : 소 폐동맥 내피세포에서 ET 생산을 자극하며 그 기전은 혈소판과 활성화된 혈소판에서 유리되는 TGF-${\beta}1$ 등의 매개물에 의한 내피세포의 자극으로 생각되며 이외에 혈소판에 의한 내피세포의 ET 생산 반응 조절(priming) 가능성도 추측할 수 있다.

• Journal of Oral Medicine and Pain
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• 제26권4호
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• pp.319-329
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• 2001

Endothelin-1 (ET-1) is a recently discovered potent vasoconstrictive peptide. It was first identified in vascular endothelial cells. ET-1 is a 21-amino acid peptide and elicits systemic effects such as stimulation of the production of atrial natriuretic peptide and release of aldosterone and corticosterone. In this study, to examine the role of ET-1 in the bone metabolism, effect of ET-1 on the proliferation and activity of osteoblastic cells was studied using HOS cells as osteoblast model. ET-1 dose-dependently increased the cell proliferation as determined by cell counting and MTT reduction assay after 48hr treatment. Alkaline phosphatase activity was inhibited by ET-1 and showed significant inhibition by 50 and 100 nM ET-1. ET-1 increased NBT reduction by HOS cells dose-dependently showing that ET-1 may increase the superoxide production by osteoblasts. Nitrite concentration in the media of HOS cell culture without cytokine stimulation was negligible and unaffected by ET-1 after 48hr treatment. Finally, after collection and concentration of conditioned media, gelatinase activity produced by HOS cells was determined by zymography. HOS cells can produce and secrete the gelatinase (gelatinase A type as determined by molecular weight of about 65,000) into culture media, however, ET-1 had no effect on the gelatinase activity. These findings suggest that ET-1 may have diverse effects on the proliferation and differentiation of osteoblasts, therefore, it may play an important role in bone metabolism.

• BMB Reports
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• 제46권7호
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• pp.364-369
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• 2013

Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia-associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITF-siRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.386-392
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• 2012

The endothelin (ET) signaling pathway controls many physiological processes in myocardium and often becomes upregulated in heart diseases. The aim of the present study was to investigate the effects of ET receptor upregulation on the contractile function of adult ventricular myocytes. Primary cultured adult rat ventricular myocytes were used as a model system of ET receptor overexpression in the heart. Endothelin receptor type A ($ET_A$) or type B ($ET_B$) was overexpressed by Adenoviral infection, and the twitch responses of infected ventricular myocytes were measured after ET-1 stimulation. Overexpression of $ET_A$ exaggerated positive inotropic effect (PIE) and diastolic shortening of ET-1, and induced a new twitch response including twitch broadening. On the contrary, overexpression of $ET_B$ increased PIE of ET-1, but did not affect other two twitch responses. Control myocytes expressing endogenous receptors showed a parallel increase in twitch amplitude and systolic $Ca^{2+}$ in response to ET-1. However, intracellular $Ca^{2+}$ did not change in proportion to the changes in contractility in myocytes overexpressing $ET_A$. Overexpression of $ET_A$ enhanced both systolic and diastolic contractility without parallel changes in $Ca^{2+}$. Differential regulation of this nature indicates that upregulation of $ET_A$ may contribute to diastolic myocardial dysfunction by selectively targeting myofilament proteins that regulate resting cell length, twitch duration and responsiveness to prevailing $Ca^{2+}$.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.223-228
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• 2010

The collecting duct endothelin (ET) system, which involves ET-1 and its two receptors, may play a role in the regulation of renal sodium in association with the nitric oxide synthase (NOS) system. We determined whether sodium retention is associated with changes in the endothelin and NOS systems at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndromes. On day 7 after puromycin aminonucleoside (PAN) injection, urinary sodium excretion was decreased, ascites had developed, and there was a positive sodium balance. ET-1 mRNA expression was increased in the inner medulla of the kidney, whereas protein expression of ET receptor type B ($ET_BR$) was unchanged. The expression of neuronal NOS (nNOS) was decreased in the inner medulla. On day 14, urinary sodium excretion was unchanged compared with controls. The expression of $ET_BR$ increased, while nNOS expression in the inner medulla was comparable to controls. These findings suggest that decreased nNOS plays a role in the development of sodium retention in the nephrotic syndrome. Recovery of nNOS and increased renal $ET_BR$ synthesis may promote sodium excretion in later stages of the nephrotic syndrome (on day 14).

• 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.

• Tuberculosis and Respiratory Diseases
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• 제45권2호
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• pp.360-368
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• 1998

배 경: Endothelin(ET)은 혈관내피세포, 기도상피세포등에서 분비되고, 혈판 및 기도를 수축시키는 작용외에도 섬유아세포를 증식시키는 기능을 가지고 있다. 한편 미만성간질성폐질환은 염증세포의 침윤과 섬유화를 특정으로 하는 질환이며 이러한 질환을 가전 환자에서 혈장 및 기관지폐포세척액내의 ET 농도가 증가한다는 보고가 있었다. 또 폐혈관손상이 있는 경우 폐순환을 통한 ET의 제거율이 감소하기 때문에 ET의 동정맥비가 증가한다는 보고가 있었다. 이에 저자등은 미만성간질성폐질환 환자에서 혈장 ET 농도가 증가하는지, 또 증가한다면 어떠한 기전에 의하여 증가하는 지를 알고자 본 연구를 시행하였다. 방 법: 도플러심초음파상 폐동맥고혈압이 없는 미만성간질성폐질환 환자 17명과 정상대조군 11명을 대상으로 혈장, 요 중 및 기관지폐포세척액내의 ET 농도를 측정하였고, 또 이들의 ET 동-정맥 비와 요배설율을 구하였다. 성 적: 동맥혈, 정맥혈, 요 중 및 기관지폐포세척액내의 ET 농도는 미만성간질성폐질환군에서 대조군보다 유의하게 증가하였고 (P<0.05), ET의 동-정맥 비와 요배설율에는 유의한 차이가 없었다 (P>0.05). 결 론: 이상의 결과, 미만성간질성폐질환 환자의 혈장, 요 중 및 기관지폐포세척액내의 Endothelin농도는 대조군에 비해 유의하게 증가되어 있었고, 혈장 ET농도 증가의 기전은 폐실질에서의 분비증가로 사료되었다.