• 대한약리학회지
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• 제22권1호
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• pp.24-33
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• 1986

본 연구에서는 개구리(Rana nigromaculata)의 피부에 있어서 전위차(PD), 단락전류(SCC) 및 total skin conductance(TSC)에 미치는 제종 adrenergic agonist 및 그 차단제의 영향을 관찰하여 개구리 피부에 adrenoceptors의 존재를 확인하고 Na 수송에 있어 그들의 역할을 구명코자 하였다. 1.Norepinephrine(NE, $6{\times}10^{-8}-6{\times}10^{-5}M$), phenylephrine($PE,5{\times}10^{-6}-5{\times}10^{-4}M$)의 PD 및 epinephrine(Epi, $5.5{\times}10^{-7}-5.5{\times}10^{-5}M$)의 PD 및 SCC 증가효과는 약물의 투여농도에 비례하였으며, Epi의 최대효과는 NE나 PE의 것보다 약하였다. 2. 이러한 PD 및 SCC의 증가효과는 alpha 1 adrenoceptor 차단체인 prazosin $2{\times}10^{-6}M$에 의해서 억제되었으며, 특히 Epi의 증가효과는 불가역성 alpha receptor 차단제인 phenoxybenzamine $3.3{\times}10^{-5}M$에 의하여 완전히 차단되며 대량의 Epi에 의해서는 PD 및 SCC의 감소를 초래하였다. 3. Beta adrenoceptor agonist인 isoproterenol$(5{\times}10^{-7}-5{\times}10^{-6}M)$에 의해 농도증가에 비례한 PD 및 SCC의 감소가 일어났으며, 이는 선택적 bete receptor 차단제인 propranolol $4{\times}10^{-6}M$에 의해 차단되었다. 또한 Epi의 PD 및 SCC 증가효과는 propranolol $4{\times}10M$에 의하여 강화됨을 볼 수 있었다. 4. Alpha 2 adrenoceptor agonist인 clonidine 및 guanabenz도 PD 및 SCC의 증가를 가져왔으며 이러한 효과는 alpha 2 receptor 차단제인 yohimbine에서 보다 Alpha 1 receptor 차단제인 prazosin에 의해 더 잘 억제되었다. 이상 실험의 결과 개구리 복부피부에도 포유동물에서와 같이 adrenergic alpha 및 beta receptor가 존재하며 alpha receptor는 PD 및 SCC의 증가를, beta receptor는 PD 및 SCC의 감소를 매개하여, 개구리 피부의 Na 수송에 있어 adrenergic system이 중요한 조절작용을 하고 있음을 알 수 있었다. 그러나 여기에 관여하는 alpha receptor는 다른 포유류에서와 같이 alpha 1 및 alpha 2 adrenoceptor로 구분할 수는 없었다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4949-4954
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• 2015

The present study was planned to investigate the role of sex hormone receptor gene expression in the pathogenesis of hepatocellular carcinoma (HCC). Adult male Wistar rats were divided into seven groups. Group (1) was negative control. Groups (2), (5), (6), and (7) were orally administered with N-nitrosodiethylamine for the induction of HCC, then group (2) was left untreated, group (5) was orally treated with curcumin, group (6) was orally treated with carvacrol, and group (7) was intraperitoneally injected with doxorubicin, whereas groups (3) and (4) were orally administered only curcumin and carvacrol, respectively. The HCC group showed significant upregulation in the androgen receptor (AR) and the estrogen receptor-alpha ($ER{\alpha}$) gene expression levels in the liver tissue. On the contrary, HCC groups treated with either curcumin or carvacrol showed significant downregulation in AR and $ER{\alpha}$ gene expression levels in the liver tissue. In conclusion, the obtained data highlight that both AR and $ER{\alpha}$ but not estrogen receptor-beta ($ER{\beta}$) gene expression may contribute to the male prevalence of HCC induced in male rats. Interestingly, both curcumin and carvacrol were found to have a promising potency in alleviating the male predominating HCC.

• Molecules and Cells
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• 제38권4호
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• pp.356-361
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• 2015

Mitochondrial dysfunction is associated with insulin resistance and diabetes. We previously showed that retinoid X receptor ${\alpha}$ ($RXR{\alpha}$) played an important role in transcriptional regulation of oxidative phosphorylation (OXPHOS) genes in cells with mitochondrial dysfunction caused by mitochondrial DNA mutation. In this study, we investigated whether mitochondrial dysfunction induced by incubation with OXPHOS inhibitors affects insulin receptor substrate 1 (IRS1) mRNA and protein levels and whether $RXR{\alpha}$ activation or overexpression can restore IRS1 expression. Both IRS1 and $RXR{\alpha}$ protein levels were significantly reduced when C2C12 myotubes were treated with the OXPHOS complex inhibitors, rotenone and antimycin A. The addition of $RXR{\alpha}$ agonists, 9-cis retinoic acid (9cRA) and LG1506, increased IRS1 transcription and protein levels and restored mitochondrial function, which ultimately improved insulin signaling. $RXR{\alpha}$ overexpression also increased IRS1 transcription and mitochondrial function. Because $RXR{\alpha}$ overexpression, knock-down, or activation by LG1506 regulated IRS1 transcription mostly independently of mitochondrial function, it is likely that $RXR{\alpha}$ directly regulates IRS1 transcription. Consistent with the hypothesis, we showed that $RXR{\alpha}$ bound to the IRS1 promoter as a heterodimer with peroxisome proliferator-activated receptor ${\delta}$ ($PPAR{\delta}$). These results suggest that $RXR{\alpha}$ overexpression or activation alleviates insulin resistance by increasing IRS1 expression.

• The Korean Journal of Pain
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• 제22권3호
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• pp.210-215
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• 2009

Background: Several studies have indicated that a nerve injury enhances the expression of the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit (Cav ${\alpha}2{\delta}1$) in sensory neurons and the dorsal spinal cord. This study examined whether NMDA receptor activation is essential for Cav ${\alpha}2{\delta}1$-mediated tactile allodynia in Cav ${\alpha}2{\delta}1$ overexpressing transgenic mice and L5/6 spinal nerve ligated rats (SNL). These two models show similar Cav ${\alpha}2{\delta}1$ upregulation and behavioral hypersensitivity, without and with the presence of other injury factors, respectively. Methods: The transgenic (TG) mice were generated as described elsewhere (Feng et al., 2000). The left L5/6 spinal nerves in the Harlan Sprague Dawley rats were ligated tightly (SNL) to induce neuropathic pain, as described by Kim et al. (1992). Memantine 2 mg/kg (10 ul) was injected directly into the L5/6 spinal region followed by $10{\mu}l$ saline. Tactile allodynia was tested for any mechanical hypersensitivity. Results: The tactile allodynia in the SNL rats could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5 hours. The tactile allodynia in the Cav ${\alpha}2{\delta}1$ over-expressing TG mice could be reversed by an intrathecal injection of memantine 2 mg/kg at 1.5, 2.0 and 2.5 hours. Conclusions: The behavioral hypersensitivity was similar in the TG mice and nerve injury pain model, supporting the hypothesis that elevated Cav ${\alpha}2{\delta}1$ mediates similar pathways that underlie the pain states in both models. The selective activation of spinal NMDA receptors plays a key role in mediating the pain states in both the nerve-injury rats and TG mice.

• The Korean Journal of Physiology
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• 제7권2호
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• pp.67-70
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• 1973

This experiment was carried out to investigate the influence of adrenergic receptor blockade. on digitalis intoxication. The effects of adrenergic alpha and beta receptor blockade on the lethal dose of digitonin were evaluated. $LD_{50}$ and dose mortality curve of digitonin in mice pretreated with dibenzylin or propranolol hydrochloride (Inderal) were obtained. All drugs were injected subcutaneously. Digitonin toxicity was significantly decreased in mice pretreated with beta·blockade compare with alpha-blockade and control groups.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.23-23
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• 2003

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (AhR) ligands suppress 17${\beta}$-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent degradation of endogenous estrogen receptor ${\alpha}$ (ER${\alpha}$).(omitted)

• Nutrition Research and Practice
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• 제5권2호
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• pp.112-116
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• 2011

We investigated the effect of paternal folate status on folate content and expression of the folate transporter folate receptor ${\alpha}$ ($FR{\alpha}$) in rat placental tissues. Rats were mated after males were fed a diet containing 0 mg of folic acid/kg of diet (paternal folate-deficient, PD) or 8 mg folic acid/kg of diet (paternal folate-supplemented, PS) for 4 weeks. At 20 days of gestation, the litter size, placental weight, and fetal weight were measured, and placental folate content (n=8/group) and expression of $FR{\alpha}$ (n=10/group) were analyzed by microbiological assay and Western blot analysis, respectively. Although there was no difference observed in litter size or fetal weight, but significant reduction (10%) in the weight of the placenta was observed in the PD group compared to that in the PS group. In the PD group, placental folate content was significantly lower (by 35%), whereas $FR{\alpha}$ expression was higher (by 130%) compared to the PS group. Our results suggest that paternal folate status plays a critical role in regulating placental folate metabolism and transport.

• Biomolecules & Therapeutics
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• 제13권4호
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• pp.227-231
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• 2005

The estrogen receptor (ER) is activated and degraded by estrogen. We have examined ER downregulation and activation under hypoxia mimetic conditions. Cobalt chloride induced ER downregulation at 24 h of treatment. This degradation involved hypoxia-inducible factor-1$\alpha$ (HIF-1$\alpha$) as examined by using a constitutively active form of HIF-1$\alpha$, HIF-1$\alpha$/VP16, constructed by replacing the transactivation domain of HIF-1$\alpha$ with that of VP16. Western blot analysis revealed that E2-induced ER downregulation was observed within ${\~}6h$, whereas HIF-1$\alpha$/VP16-induced ER degradation was observed within 12${\~}$20h. HIF-1$\alpha$/VP16 activated the transcription of estrogen-responsive reporter gene in the absence of estrogen. These results suggest that ER downregulation and activation under hypoxia maybe mediated in part by a HIP-1$\alpha$ expression.

• 약학회지
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• 제54권2호
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• pp.102-105
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• 2010

Our previous results showed that hypoxia inducible factor-1 (HIF-1) activated estrogen receptor (ER) in the absence of ligand. In this study, we have studied the effect ER overexpression on the activation of HIF-1. ER overexpression induced transcription activation of hypoxia response element driven luciferase and vascular endothelial growth factor. As a negative control, the effect of ER on androgen receptor response element was used. Our result indicate that the two ER$\alpha$ and HIF-1 signaling pathways shares part of the activation pathway.

• Journal of Microbiology and Biotechnology
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• 제28권10호
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• pp.1589-1603
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• 2018

Twenty analogs of $[Orn^6,D-Ala^9]{\alpha}-factor$ were synthesized and assayed for their biological activities: seven analogs of $[Orn^6,X^9]{\alpha}-factor$, seven analogs of $[X^6,D-Ala^9]{\alpha}-factor$, five analogs of $[X^5,X^6,D-Ala^9]{\alpha}-factor$, and native ${\alpha}-factor$ (X = amino acids). Their biological activities (halo, gene induction, and affinity) were measured using S. cerevisiae Y7925 and LM102 and compared with those of native ${\alpha}-factor$ (100%). G protein-coupled receptor was expressed in strain LM102 containing pESC-LEU-STE2 vector. $[Dap^6,D-Ala^9]{\alpha}-factor$ with weak halo activity (10%) showed the highest receptor affinity (> 230%) and the highest gene induction activity (167%). $[Arg^6,D-Ala^9]{\alpha}-factor$ showed the highest halo activity (2,000%). The number of active binding sites per cell (about 20,000 for strain LM102) was determined using a newly-designed fluorescence-based detector, $[Arg^6,D-Ala^9]{\alpha}-factor-Edan$, with high sensitivity (12,500-fold higher than the absorption-based detector $[Orn^6]{\alpha}-factor-[Cys]_3$).