• Title/Summary/Keyword: Blocker

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cAMP-Dependent Signalling is Involved in Adenosine-Stimulated $Cl^-$ Secretion in Rabbit Colon Mucosa

  • Oh, Sae-Ock;Kim, Eui-Yong;Jung, Jin-Sup;Woo, Jae-Suk;Kim, Yong-Keun;Lee, Sang-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.4
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    • pp.521-527
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    • 1998
  • An important property of the intestine is the ability to secrete fluid. The intestinal secretion is regulated by a number of substances including vasoactive intestinal peptide (VIP), ATP and different inflammatory mediators. One of the most important secretagogues is adenosine during inflammation. However, the controversy concerning the underlying mechanism of adenosine-stimulated $Cl^-$ secretion in intestinal epithelial cells still continues. To investigate the effect of adenosine on $Cl^-$ secretion and its underlying mechanism in the rabbit colon mucosa, we measured short circuit current ($I_{SC}$) under automatic voltage clamp with DVC-1000 in a modified Ussing chamber. Adenosine, when added to the basolateral side of the muocsa, increased $I_{SC}$ in a dose-dependent manner. The adenosine-stimulated $I_{SC}$ response was abolished when $Cl^-$ in the bath solution was replaced completely with gluconate. In addition, the $I_{SC}$ response was inhibited by a basolateral Na-K-Cl cotransporter blocker, bumetanide, and by apical $Cl^-$ channel blockers, dephenylamine-2-carboxylate (DPC), 5-nitro-2-(3-phenyl-propylamino)-benzoate (NPPB), glibenclamide. Amiloride, an epithelial $Na^+$ channel blocker, and 4,4-diisothiocyanato-stilbene-2,2-disulphonate (DIDS), a $Ca^{2+}-activated$ $Cl^-$ channel blocker, had no effect. In the mucosa pre-stimulated with forskolin, adenosine did not show any additive effect, whereas carbachol resulted in a synergistic potentiation of the $I_{SC}$ response. The adenosine response was inhibited by 10 ${\mu}M$ H-89, an inhibitor of protein kinase A. These results suggest that the adenosine-stimulated $I_{SC}$ response is mediated by basolateral to apical $Cl^-$ secretion through a cAMP-dependent $Cl^-$ channel. The rank order of potencies of adenosine receptor agonists was $5'-(N-ethylcarboxamino)adenosine(NECA)>N^6-(R-phenylisopropyl)adenosine(R-$ PIA)>2-[p-(2-carbonylethyl)-phenyl-ethylamino]-5'-N-ethylcarboxaminoadenosine(CGS21680). From the above results, it can be concluded that adenosine interacts with the $A_{2b}$ adenosine receptor in the rabbit colon mucosa and a cAMP-dependent signalling mechanism underlies the stimulation of $Cl^-$ secretion.

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The Antioxidant Activities and Hair-growth Promotion Effects of Tenebrio molitor Larvae Extracts (TMEs) (갈색거저리 유충 추출물의 항산화 활성 및 모발 성장 촉진 효과)

  • Baek, Minhee;Seo, Minchul;Kim, Mi-Ae;Yun, Eun-Young;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.27 no.11
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    • pp.1269-1275
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    • 2017
  • Tenebrio molitor samples were investigated as novel biomaterials and sources of food in several recent studies. However, the insects' effects on hair growth were not sufficiently researched. To develop novel and natural materials for preventing alopecia and promoting hair growth, this study investigated the antioxidant activities and hair-growth promotion effects of TMEs. To determine the antioxidant activities, the TMEs' DPPH radical- and nitrite-scavenging activities were examined. To determine hair-growth promotion effects, proliferations of human dermal papilla cells (DPCs) and the murine fibroblast cell line NIH3T3 were evaluated by using an MTS assay. In addition, estimations were made for cell viabilities against cell death induced by dihydrotesterone (DHT) in DPCs and inhibitory effects against potassium channel blocking induced by tolbutamide (TBM) in NIH3T3 cells. The DPPH radical scavenging activity was 81.17%, and the nitrite scavenging activity was 43.69%; the activities were similar to the activities of blueberry extracts. Moreover, the TMEs promoted the proliferation of human DPCs and NIH3T3 cells, which were concentrated dependently. The TMEs prevented not only DHT-induced DPC cytotoxicity but also TBM's action as a potassium channel blocker in NIH3T3 cells. The results suggested that TME could be used as a functional therapeutic alopecia reagent, to prevent hair loss and to promote hair growth.

Regulation of $Ba^{2+}$-Induced Contraction of Murine Ureteral Smooth Muscle

  • Kim, Young-Chul;Lee, Moo-Yeol;Kim, Wun-Jae;Myung, Soon-Chul;Choi, Woong;Kim, Chan-Hyung;Xu, Wen-Xie;Kim, Seung-Ryul;Lee, Sang-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.5
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    • pp.207-213
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    • 2007
  • This study was designed to characterize ureteral smooth muscle motility and also to study the effect of forskolin(FSK) and isoproterenol(ISO) on smooth muscle contractility in murine ureter. High $K^+$(50 mM) produced tonic contraction by $0.17{\pm}0.06mN$(n=19). Neuropeptide and neurotransmitters such as serotonin($5{\mu}M$), histamine($20{\mu}M$), and carbarchol(CCh, $10{\sim}50{\mu}M$) did not produce significant contraction. However, CCh($50{\mu}M$) produced slow phasic contraction in the presence of 25 mM $K^+$. Cyclopiazonic acid(CPA, $10{\mu}M$), SR $Ca^{2+}$-ATPase blocker, produced tonic contraction(0.07 mN). Meanwhile, inhibition of mitochondria by protonophore carbnylcyanide m-chlorophenylhydrazone(CCCP) also produced weak tonic contraction(0.01 mN). The possible involvement of $K^+$ channels was also pursued. Tetraethyl ammonium chloride(TEA, 10 mM), glibenclamide($10{\mu}M$) and quinidine($20{\mu}M$) which are known to block $Ca^{2+}$-activated $K^+$ channels($K_{Ca}$ channel), ATP-sensitive $K^+$ channels($K_{ATP}$) and nonselective $K^+$ channel, respectively, did not elicit any significant effect. However, $Ba^{2+}$($1{\sim}2mM$), blocker of inward rectifier $K^+$ channels($K_{IR}$ channel), produced phasic contraction in a reversible manner, which was blocked by $1{\mu}M$ nicardipine, a blocker of dehydropyridine-sensitive voltage-dependent L-type $Ca^{2+}$ channels($VDCC_L$) in smooth muscle membrane. This $Ba^{2+}$-induced phasic contraction was significantly enhanced by $10{\mu}M$ cyclopiazonic acid(CPA) in the frequency and amplitude. Finally, regulation of $Ba^{2+}$-induced contraction was studied by FSK and ISO which are known as adenylyl cyclase activator and $\beta$-adrenergic receptor agonist, respectively. These drugs significantly suppressed the frequency and amplitude of $Ba^{2+}$-induced contraction(p<0.05). These results suggest that $Ba^{2+}$ produces phasic contraction in murine ureteral smooth muscle which can be regulated by FSK and $\beta$-adrenergic stimulation.

The Clinical Impact of β-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention

  • Jiesuck Park;Jung-Kyu Han;Jeehoon Kang;In-Ho Chae;Sung Yun Lee;Young Jin Choi;Jay Young Rhew;Seung-Woon Rha;Eun-Seok Shin;Seong-Ill Woo;Han Cheol Lee;Kook-Jin Chun;DooIl Kim;Jin-Ok Jeong;Jang-Whan Bae;Han-Mo Yang;Kyung Woo Park;Hyun-Jae Kang;Bon-Kwon Koo;Hyo-Soo Kim
    • Korean Circulation Journal
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    • v.52 no.7
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    • pp.544-555
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    • 2022
  • Background and Objectives: The outcome benefits of β-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of β-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). Methods: A total of 3,075 patients with chronic CAD were included from the Grand Drug-Eluting Stent registry. We analyzed β-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (β-blockers vs. no β-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of β-blockers. Results: During a median (interquartile range) follow-up of 3.1 (3.0-3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, β-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63-1.24), all-cause death (HR, 0.87; 95% CI, 0.60-1.25), and MI (HR, 1.25; 95% CI, 0.49-3.15). In subgroup analysis, β-blockers were associated with a lower risk of all-cause death in patients with previous MI and/or revascularization (HR, 0.38; 95% CI, 0.14-0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of β-blockers. Conclusions: Overall, β-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of β-blockers may exist for patients with previous MI and/or revascularization.

Molecular Dynamics Simulation of Enantioselectivity in Metoprolol in complex

  • Jang, Seok-Young;Park, Kyung-Lae
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.356.3-357
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    • 2002
  • Metoprolol (MT) is one kinds of adrenergic beta-blockers. Its (S)-enantiomer is known to be more active than the (R). Recently. the x-ray structure of beta-blocker. (S)-propranolol (a-naphthyl analogue), complexed in a mould fungal cellulase. Cel7A. was reported and the (R)-form did not build any complex. And in our previous study the conformation and stability of MT in carboxymethylated beta-cyclodextrin (BCD) complex was determined by NMR. HPLC, UV and electrophoresis measurement. (omitted)

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Minimum Requirement of Front-End in W-CDMA RF Receiver (W-CDMA RF 수신기 전단의 최소 요구사항)

  • 심재성;육종관;박한규;하동인
    • Proceedings of the Korea Electromagnetic Engineering Society Conference
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    • 2002.11a
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    • pp.205-208
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    • 2002
  • This paper presents a quantitative analysis on the intermodulation product between transmitter W-CDMA leakage signal and receiver out of band blocker, and proposes design guide lines for overcoming the effect in receiver design. Our analysis shows that duplexer isolation, attenuation and LNA IIP3 are mainly responsible for the 3rd order intermodulation product. Analysis also shows that LNA IIP3 required for meeting 3GPP TS 34.121 specification is about 1 ㏈m with duplexer isolation of 50 ㏈ and duplexer attenuation of 24㏈.

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Synthesis of Antithypertensive Agents via Couping Reaction of Benzothiazepinone and 1,4-Dihydropyridine Derivatives

  • Ham, Won-Hun;Yang, Jae-Gwon;Lim, Tae-Gyun;Jung, Yun-Ho;Chung, Yun-Sung
    • Archives of Pharmacal Research
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    • v.17 no.2
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    • pp.119-123
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    • 1994
  • The synthesis of 3a, 3b, 7a fro Benzpthiazepinone and 1,4-dihyropyridine derivatives is described. Benzothiazepinone nad 1,4-dihydropyridine derivatives were prepared according to literature procedure. The key reactions involve esterification and amidation of benzothize-pinone nad 1,4-dihydropyridine derivatives.

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Reanalysis of Dissimilation in Harmonic Phonology

  • Oh, Kwan-Young
    • English Language & Literature Teaching
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    • v.8 no.2
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    • pp.91-104
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    • 2003
  • The purpose of this paper is to show that when we consider the analytical ways of Dissimilation, it becomes clear that it is insufficient to deal with it in just linear and nonlinear ways. Thus within a new framework to be introduced in this paper, Harmonic Phonology, we will reanalyze the phenomenon. We will also consider how the Obligatory Contour Principle (hereinafter, OCP) is used as both rule trigger and rule blocker in rule application, and works as a universal constraint, that is, a filtering device of ill formed representation. As we also consider it under the new framework, we can show the application position and motivation of rules appropriately and represent the phenomenon synthetically. (Yosu National University)

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