• Journal of Korean Neurosurgical Society
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• 제64권5호
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• pp.716-725
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• 2021

Objective : The anti-tumor effect of the beta-adrenergic receptor antagonist propranolol in breast cancer is well known; however, its activity in glioblastoma is not well-evaluated. The Notch-Hes pathway is known to regulate cell differentiation, proliferation, and apoptosis. We investigated the effect of propranolol to human glioblastoma cell lines, and the role of Notch and Hes signaling in this process. Methods : We performed immunohistochemical staining on 31 surgically resected primary human glioblastoma tissues. We also used glioblastoma cell lines of U87-MG, LN229, and neuroblastoma cell line of SH-SY5Y in this study. The effect of propranolol and isoproterenol on cell proliferation was evaluated using the MTT assay (absorbance 570 nm). The impact of propranolol on gene expression (Notch and Hes) was evaluated using real-time polymerase chain reaction (RT-PCR, whereas protein levels of Notch1 and Hes1 were measured using Western blotting (WB), simultaneously. Small interfering RNA (siRNA) was used to suppress the Notch gene to investigate its role in the proliferation of glioblastoma. Results : Propranolol and isoproterenol caused a dose-dependent decrease in cell proliferation (MTT assay). RT-PCR showed an increase in Notch1 and Hes1 expression by propranolol, whereas WB demonstrated increase in Notch1 protein, but a decrease in Hes1 by propranolol. The proliferation of U87-MG and LN229 was not significantly suppressed after transfection with Notch siRNA. Conclusion : These results demonstrated that propranolol suppressed the proliferation of glioblastoma cell lines and neuroblastoma cell line, and Hes1 was more closely involved than Notch1 was in glioblastoma proliferation.

• 대한약리학회지
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• 제24권1호
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• pp.83-92
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• 1988

세포질 내 칼슘 농도의 증가는 다형핵 백혈구의 산화성 대사를 자극하는 주요 인자로 여겨지고 있다. 활성화된 다형핵 백혈구로부터 lysosomal enzyme의 유리는 세포내 cyclic nucleotide농도에 따라 조절될 수 있지만 신경전달물질과 ${\beta}$-아드레날린 또는 무스카린성 수용체의 결합에 따른 그밖의 반응은 아직도 분명하지 않다. 덧붙여, ${\alpha}$-아드레날린성 수용체의 중개에 의한 다형핵 백혈구의 기능은 알려져 있지 않다. Atropine, phentolamine과 propranolol은 활성화된 다형핵 백혈구의 칼슘흡수, superoxide 생성, NADPH oxidase 활성도 그리고 식작용을 억제하였으며, 이에 반하여 carbachol과 isoproterenol은 활성화된 세포의 반응을 약간 더 자극하였다. Carbachol또는 isoproterenol 의하여 항진된 superoxide 생성은 각각 그들의 길항제인 atropine과 propranolol 의하여 억제되었다. 활성화된 다형핵 백혈구의 반응은 chlorpromazine, verapamil과 dantrolene에 의하여 억제되었으나 lithium에 의 하여 약긴 항진되었다. 한편 chlorpromazine과 dibucaine은 NADPH oxidase 활성도에 영향을 주지 않았다. Atropine, phentolamine과 propranolol은 칼슘에 의존적인 식작용을 억제 하였다. 이상의 결과로부터 atropine, phentolamine과 propranolol은 칼슘 유입을 억제하고 자율 신경계의 수용체와 연관이 있는 NADPH oxidase계에 직접 작용함으로써 활성화된 다형핵 백혈구로부터 superoxide 생성을 억제할 것으로 시사되었다.

• 대한약리학회지
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• 제29권1호
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• pp.65-72
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• 1993

자외선조사는 흰쥐흉부대동맥의 휴지기장력에 거의 영향을 미치지 못했으나, phenylephrine으로 수축된 표본에서는 자외선조사로 내피세포가 존재하면 수축반응을, 내피세포가 제거되면 이완반응이 나타났다. 이 수축반응은 조사시간의 길이($10{\sim}320$초)에 비례하여 증가하였으나 이완반응은 그렇지 못하였다. 내피세포 존재표본에서 자외선의 수축반응은 phenylephrine농도의 증가($10^{-7}{\sim}10^{-5}M$) 그리고 $acetylcholine(10^{-6}M)$, $isoproterenol(10^{-7}M)$ 및 $nitroglycerin(3.5{\times}10^{-8} M)$의 추가투여시 크게 강화되었다. 그러나 $phentolamine(10^{-6}M)$ 또는 $LY83583(10^{-7},10^{-6}M)$의 추가투여시에는 자외선 수축반응이 억제 또는 이완반응으로 역전되었다. 내피세포 제거표본에서의 자외선 이완반응은 phenylephrine농도의 증가 그리고 isoproterenol, nitroglycerine, phentolamine 및 LY83583의 추가투여시 유의하게 감약되었다. 이상의 성적은 흰쥐 적출 흥부대동맥에서 자외선조사는 내피세포 존재유무에 따라 수축과 이완반응이 각각 나타나며, 수축반응은 자외선에 의한 EDRF 유리억제 또는 부분적으로 어떤 EDCF와도 관련이 있음을 시사하고 있다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.215.2-216
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• 2002

• BMB Reports
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• 제47권10호
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• pp.587-592
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• 2014

We investigated the effects of ${\beta}$-adrenergic activation on bone marrow adiposity and on adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). C57BL/6 mice were subjected to a control (CON), high calorie (HIGH) or low calorie (LOW) diet for 12 weeks. In each group, mice were treated with vehicle (VEH) or propranolol. The number of adipocytes per area bone marrow was increased in LOWVEH and HIGHVEH mice compared with CONVEH mice, which was attenuated by propranolol. Isoproterenol increased lipid droplet accumulation and adipogenic marker gene expression in 3T3-L1 preadipocytes and mouse BMSCs, which were blocked by propranolol. Conditioned medium obtained from MC3T3-E1 osteoblasts suppressed adipogenic differentiation of 3T3-L1 cells, which was significantly attenuated by treatment of MC3T3-E1 cells with isoproterenol. These data suggest that ${\beta}$-adrenergic activation enhances bone marrow adipogenesis via direct stimulation of BMSCs adipogenesis and indirect inhibition of osteoblast anti-adipogenic potential.

• 약학회지
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• 제38권3호
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• pp.238-249
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• 1994

The purpose of this research was to investigate effects of baicalin on the differentiation of preadipocytes, 3T3-L1, and to characterize the action of baicalin that affect the responses of 3T3-L1 cells during differentiation. In various culture conditions, effects of baicalin and adrenoreceptor agonists such as phenylephrine(PE) and isoproterenol(IPR) on cell differentiation were examined. Also, effects of the drugs on differentiation, triglyceride(TG) contents, expression of insulin receptor, cAMP contents, the cytosolic $Ca^{2+}$ levels, and amount of calmodulin(CaM) were examined. The results suggest that baicalin has adrenergic receptor blocking activity during the process of differentiation of 3T3-L1 cells and that in the early stage of the adipose conversion, the effect of baicalin on the adipocyte differentiation is mediated by the regulation of insulin receptor expression, but by alterations of the cAMP and the calcium metabolism in the late stage. These results also suggest that the action of baicalin may be significant in the lipid metabolism, lipogenic and lipolytic pathways, of adipose cells.

• 약학회지
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• 제35권4호
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• pp.341-347
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• 1991

It was reported that protein carboxymethylation is involved in amylase secretion of parotid gland by isoproterenot. It was also suggested that a small part of the total cellular protein carboxymethylation is directly involved in pancreatic enzyme secretion. On the contrary, other authors reported that there is no relationship between protein carboxymethylation and secretion in pancreas and parotid gland. In recent study, it was proposed that a methyl acceptor protein plays a limited modulatory role in the coupling of cytosolic $Ca^{++}$ accumulation and exocytosis. In this study, the effects of cholinergic and adrenergic agents on the activities of protein methylase II in pancreatic tissues were examined to test the relationship between protein methylation and pancreatic secretion. The results are as follows. The activity of amylase was slightly increased at the concentration of $10^{-5}$ M of isoproterenol and norepinephrine. The activities of protein methylase I and II were decreased by isoproterenol and norepinephrine, but the activities of protein methylase III were hardly changed. The cholinergic stimulants acetylcholine and carbachol at a concentration of $10^{-5}$ M increased the activities of protein methylase I and decreased the activitiy of protein methylase III compared with control.

• 대한수의학회지
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• 제45권4호
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• pp.537-544
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• 2005

We have examined distribution and expression of caveolin-3 (cav-3), one of three caveolin isoforms from 16-wks-old spontaneously hypertensive rats (SHR) compared with age-matched control wistar-kyoto (WKY) rats. The expression of cav-3 was increased, whereas expression of PKB/Akt and calcineurin (Cn) was not changed in cardiac tissues of SHR compared to WKY rats. Interestingly, expression of cav-3, PKB/Akt and Cn were decreased in plasma membrane fraction in SHR compared to WKY rats. In H9c2 cardiomyoblast cells treated with phenylephrine ($50{\mu}M$, 48hr) or isoproterenol ($10{\mu}M$, 48hr), the expression of cav-3 was markedly enhanced compared to nontreated cells. Upon immunofluorescence analysis, cav-3 was localized in plasma membrane of control H9c2 cells. However phenylephrine or isoproterenol treatment caused translocation of cav-3 to perinuclear region. These results suggest that cav-3 plays as positive regulators in the development of hypertrophy in cardiac tissues of SHR rats.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.467-477
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• 2001

We examined astrocyte regional heterogeneity in their morphological changes in response to various stimuli. Astrocytes were cultured from six different neonatal rat brain regions including cerebral cortex, hippocampus, cerebellum, mid brain, brain stem and hypothalamus. Astrocyte stellation was induced by serum deprivation and the maximum stellation in different regional astrocytes was achieved after 2 h. After 24 h, in all astrocyte cultures, the level of stellation returned to their original level. Cerebellar or hypothalamic astrocytes were the most or the least sensitive, respectively, to serum deprivation. The order of maximum sensitivity to serum deprivation among different regional astrocytes was: cerebellum＞mid $brain{\ge}hippocampus,\;brain\;stem{\ge}cerebral$ cortex＞hypothalamus. Isoproterenol-induced astrocyte stellation was also examined in different regional astrocytes, and similar order of maximum sensitivity as in serum deprivation was observed. Next a possible developmental effect on astrocyte morphological changes was examined in cerebral cortex and cerebellum astrocytes cultured from postnatal day 1 (P1), P4 and P7 rat brains. A much higher sensitivity of cerebellum astrocytes to serum deprivation as well as isoproterenol treatment was consistently observed in P1, P4 and P7-derived astrocytes compared to cerebral cortex astrocytes. The present study demonstrates different regional astrocytes maintain different levels of morphological plasticity in vitro.

• 대한약리학회지
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• 제11권2호
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• pp.29-40
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• 1975

1. 척수가토(脊髓家兎)에서 nicotine, DMPP, McN-A-343, AHR-602, tyramine, angiotensin및 neostigmine에 의한 심박증가(心搏增加)의 작용점(作用點)을 조사(調査)하였다. 2. 상기약물(上記藥物)에 의한 심박증가(心搏增加)는 reserpine 처리가토(處理家兎)에서는 대단히 약(弱)하였고, Propranolol 투여후(投與後)에는 거의 나타나지 않았다. 3. Tetrodotoxin, guanethidine은 isoproterenol, nicotine, DMPP, tyramine에 의한 심박증가(心搏增加)에는 영향(影響)을 미치지 않았으나 McN-A-343, AHR-602, angiotensin, neostigmine에 의한 심박증가(心搏增加)는 이를 현저(顯著)히 약화(弱化)시켰다. 4. Nicotine, DMPP의 심박증가(心搏增加)는 chlorisondamine으로 McN-A-343, AHR-602의 심박증가(心搏增加)는 atropine으로 각각(各各) 억제(抑制)되었다. 5. Isoproterenol, nicotine, DMPP, McN-A-343, tyramine, angiotensin, neostigmine은 적당량(適當量)을 우심방내(右心房內)에 주입(注入)하였을때 이들을 이정맥내(耳靜脈內)에 주사(注射)하였을 때와 비슷한 반응(反應)을 일으킬 수 있었다. 그러나 AHR-602 우심방내(右心房內) 주입(注入)은 유의(有意)한 심박증가(心搏增加)를 일으키지 않았다. 6. Nicotine, DMPP, neostigmine은 우심방내(右心房內) 주입시(注入時)는 현저(顯著)한 심박증가(心搏增加)를 일으켰으나, 동량(同量)을 우심실내(左心室內)에 주입(注入)하였을때는 증가(增加)를 일으키기 않았다. Isoprotereool 및 tyramine에 대한 반응(反應)은 우심실내(右心室內) 주입(注入)보다도 우심방내(右心房內) 주입시(注入時) 훨씬 컸다. 7. McN-A-343, angiotensin의 우심실내(右心室內) 주입시(注入時)는 우심방내(右心房內) 주입시(注入時)보다도 훨씬 현저(顯著)한 심박증가(心搏增加)를 일으켰고, AHR-602의 우심실내(左心室內) 주입(注入)도 현저(顯著)한 반응(反應)을 일으켰다. 8. Nicotine, DMPP, tyramine은 심장(心臟)의 aenergic nerve의 말단(末端) 또는 extraneuronal norepinephrine-store에 작용(作用)하여, Mcn-A-343, AHR-602, angiotensin은 심장(心臟)의 adrenergic nerve에 작용(作用)하여 심박증가(心搏增加)를 일으키며, nicotine, DMPP, tyramine, neostigmine의 작용점(作用點)은 주(主)로 우심방(右心房)에 McN-A-343, AHR-602, angiotenisin의 작용점(作用點)은 주(主)로 우심실(右心室)에 존재(存在)하는것으로 추론(推論)하였다.