• Title/Summary/Keyword: NO/cGMp

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Red Ginseng Saponin Fraction A Isolated from Korean Red Ginseng by Ultrafiltration on the Porcine Coronary Artery

  • Jung, Young-Hyun;Park, Kwang-Yeol;Jeon, Jin-Hong;Kwak, Yi-Seong;Song, Yong-Bum;Wee, Jae-Joon;Rhee, Man-Hee;Kim, Tae-Wan
    • Journal of Ginseng Research
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    • v.35 no.3
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    • pp.325-330
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    • 2011
  • Red ginseng saponin fraction-A (RGSF-A) contains a high percentage of panaxadiol saponins that were isolated from Korean red ginseng by ultrafiltration. The aim of this study was to elucidate the effects of RGSF-A on the porcine distal left anterior descending (LAD) coronary artery. The relaxant responses to RGSF-A were examined during contractions induced by 100 nM U46619 (9,11-dideoxy-9a,11a-methanoepoxy-prostaglandin F2a), a stable analogue of thromboxane A2. RGSF-A dose-dependently induced biphasic (fast- and slow-) relaxation in the distal LAD coronary artery in the presence of an intact endothelium. The fast-relaxation was quickly achieved in a minute, and then the slow-relaxation was slowly developed and sustained for more than thirty minutes after the administration of RGSF-A. The slow-relaxation had a tendency to be bigger than the fast-relaxation. Fast relaxation induced by RGSF-A was almost blocked by $N_{\omega}$-Nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase synthase inhibitor and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylate cyclase inhibitor. However slow relaxation induced by RGSF-A was only partially inhibited by L-NAME and ODQ. In the endothelium-removed ring, RGSF-A evoked only slowrelaxation to a certain extent. These data suggest that RGSF-A induced both endothelium dependent fast- and slow-relaxation and endothelium independent slow-relaxation in the porcine distal LAD coronary artery. The endothelium dependent fast-relaxation is mediated by the nitric oxide (NO)-cGMP pathway, and the endothelium dependent slow-relaxation is at least partially mediated by the NO-cGMP pathway. However, the endothelium-independent slow-relaxation remains to be elucidated.

Phototransduction and Visual Cycle in the Ascidian Tadpole Larva

  • Kusakabe, Takehiro;Nakashima, Yuki;Kusakabe, Rie;Horie, Takeo;Kawakami, Isao;Yoshida, Reiko;Inada, Kyoko;Nakagawa, Masashi;Tsuda, Motoyuki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.37-40
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    • 2002
  • Ascidians are lower chordates, and their tadpole-like larvae share a basic body plan with vertebrates. To study photoreceptive systems in ascidians, we have isolated and characterized cDNA clones for three opsins, five G protein ${\alpha}$ subunits (G${\alpha}$), catalytic and regulatory subunits of cGMP phosphodiesterase (PDE), and arrestin from the ascidian Ciona intestinalis tadpole larva. Ci-opsin1 and Ci-opsin2 are vertebrate-type opsins, while Ci-opsin3 is a retinal photoisomerase similar to retinochrome and mammalian RGR. Both Ci-opsin1 and arrestin are specifically localized in the photoreceptor cells of the ocellus, whereas Ci -opsin2 is not expressed in the photoreceptors, but is co-localized in another population of neurons in the brain with PDE (Ci-PDE9 and Ci-PDE$\delta$). Ci-opsin3 is present in the entire region of the brain. Though five different cDNAs encoding Ga have been cloned, no transducin-type G protein has been found yet. Interestingly, one of G${\alpha}$i isoform is conspicuously expressed in the entire region of the brain. The Ci-opsin3 gene expression was observed in a broad area of the brain vesicle as well as in the visceral ganglion. Genes encoding ascidian homologs of CRALBP and ${\beta}$-CD, whose function is required for the mammalian visual cycle, are co-expressed with Ci-opsin3 in the brain vesicle and visceral ganglion. Localization of Ci-opsin3, CRALBP, and ${\beta}$-CD in a broad area of the brain suggests that the brain of the ascidian larva has a visual cycle system similar to that of the vertebrate RPE. Based on these data, we discuss the evolution of vertebrate visual systems.

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[$Ca^{2+}-activated\;Cl^-$ Current in Gastric Antral Myocytes

  • Lee, Moo-Yeol;Bang, Hyo-Weon;Uhm, Dae-Yong;Rhee, Sang-Don
    • The Korean Journal of Physiology
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    • v.28 no.2
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    • pp.143-150
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    • 1994
  • The whole-cell mode of the patch clamp technique was used to study $Ca^{2+}-activated\;Cl^-\;current$ $(I_{Cl_{Ca}})$ in gastric antral myocytes. Extracellular application of caffeine evoked $Ca^{2+}-activated\;current$. In order to isolate the chloride current from background current, all known systems were blocked with specific blockers. The current-voltage relationship of caffeine-induced current showed outward rectification and it reversed at around $E_{Cl^-}$. The shift of reversal potential upon the alteration of external and internal chloride concentrations was well fitted with results which were calculated by the Nernst equation. Extracellular addition of N-phenylanthranilic acid and niflumic acid which are known anion channel blockers abolished the caffeine induced current. Intracellular application of a high concentration of EGTA also abolished this current. Application of c-AMP, c-GMP, heparin, or $AIF^-_4$ made no remarkable changes to this current. Sodium replacement with the impermeable cation N-methylglucamine or with $Cd^{2+}$ rarely affected this current. From the above results it is suggested that the caffeine induced current was a $Cl^-$ current and it was activated by intracellular $Ca^{2+}$.

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Gel Type Formulation Utilizing Polymer-Surfactant Interaction (폴리머와 계면활성제의 상호작용을 이용한 젤타입 제형의 제조)

  • Kim, Dong-Joo;Kang, Tae-Jun;Lee, Cheon-Koo;Lee, Jung-No
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.1 s.60
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    • pp.7-10
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    • 2007
  • The interaction between polymers and surfactants was investigated by means of rheological and surface tension measurements. The polymers used in this study were acrylates/$C_{10-30}$ alkyl acrylate crosspolymer (AC) and ammonium acryloyldimethyltaurate/VP copolymer (AV). And the surfactants were PEG-40 hydrogenated castor oil (HC) and polysorbate 60 (P60). HC and P60 made the micelles intervening between AC polymers, resulting in the increase of viscosity. However, HC showed a similar behavior over the wider range of surfactant concentration than P60. Regarding of surface tensions in the same range of surfactant concentration, AC/HC solution showed the area of increasing surface tension with surfactant concentration in contrast to the AC/P60 solution showing no increasing area. It is assumed that the micelles between AC/HC were formed so cooperatively and strongly that the surfactants located at the surface originally moved to the micelles.

Toward a More Complete Understanding of the Effects of Korean Ginseng (Panax ginseng) on Blood Pressure (고려인삼의 혈압에 미치는 영향에 대한 이해)

  • Nam, Ki Yeul;Yang, Byung Wook;Shin, Wang Soo;Park, Jong Dae
    • Korean Journal of Pharmacognosy
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    • v.48 no.2
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    • pp.97-107
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    • 2017
  • There is no doubt that the effect of ginseng on blood pressure could be different depending upon the type of ginseng employed for the experiment and methodology, thereby can exert bilateral modulatory activity on blood pressure. It has been reported that ginseng induced no significant change in blood pressure in those subjects with normal blood pressure, but had a normalizing effect on the subjects with abnormal blood pressure. Especially, experimental evidence indicates that ginsenoside Rg3, a major component of red ginseng, has been found to lower blood pressure, which is mediated by release of endothelium-derived NO, enhancing the accumulation of cGMP in the rat aorta. This clinical results further support the beneficial effect of Korean ginseng on blood pressure elucidated by animal experiment. As expected, a multicentric non-controlled clinical study shows that the effect of ginseng consumption has been found to normalize blood pressure in hypertensive or hypotensive individuals as compared to virtually no effect in normotensives. In addition, ginseng has been known to exhibit blood pressure decreased with no significant side effect and deteriorated QOL during the combination therapy of ginseng and anti-hypertensive drugs. This review provides a comprehensive overview on the effects of Korean ginseng on blood pressure.

The Effects of Endogenously and Exogenously Induced Nitric Oxides on the Nociperception of Rats (내.외인성으로 유도된 Nitric Oxide가 흰쥐의 통각전달에 미치는 효과)

  • 방준석;류정수;신창열;양성준;송현주;박전희;제현동;손의동;허인회
    • YAKHAK HOEJI
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    • v.45 no.1
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    • pp.116-124
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    • 2001
  • Nitric oxide is a labile, gaseous, broad spectrum second messenger that used in various tissues and cells. If it is induced by endogenously and exogenously in the neuronal cells, it is able to mediate analgesia or hyperalgesia at the periphery and in the spinal level respectively. This dual role of nitric oxide in the sensory system is very intriguing but has not been fully understood yet. In this experiment, acetylcholine (300 $\mu$g/paw), sodium nitroprusside (600 $\mu$g/paw), and L-arginine (300 $\mu$g/paw) represented antinociceptive effect to noxious topical stimulus, but pronociceptive responses followed by spinally application (20$\mu$g/5$\mu$l, 10$\mu$g/3$\mu$l, 500$\mu$g/5$\mu$l respectively). Calcium ion is critical element which activates nitric oxide synthase, therefore verapamil (300 $\mu$g/paw) and NOS inhibitor (20 mg/kg, L-NAME or L-NOArg) are injected into right hind paw (i.pl.). When verapamil is combined with NOS inhibitors analgesic effects through NO-cGMP pathway are inhibited as compared with ACh alone. Diluted formalin (2.5%), when injected into rats'hind paw (0.05 ml), elicited a biphasic algesic responses and nitric oxide had an analgesic effect on both $A\delta$ and C sensory nerve fibers which manipulate the phases respective1y. Nitric oxides, which produced from constitutive nitric oxide synthase, activated cyclooxygenase-type I and then prostaglandins are produced from them. So, indomethacin and ibuprofen, inhibitors of COX$_1$enzyme, when pretreated intraperitoneally (100 mg/kg) could reduce the hyperalgesic state. From these results, it is possible to imagine that the intrathecally administered NO donors expressed hyperalgesia through both long-term potentiation mechanism and arachidonic acid-prostaglandin cascade.

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N-Methyl-D-Aspartate (NMDA) Receptor Antagonistic Effect and Ginsenoside Content of Panax ginseng C. A. Meyer Cultivar Root Extracts (인삼 품종별 뿌리 추출물의 NMDA 수용체 길항 효과 및 진세노사이드 함량)

  • Lee, Seung Eun;Kim, Jang Uk;Jeong, Hyeon Soo;Choi, Je Hun;Ji, Yun Jeong;Kim, Hyung Don;Jang, Gwi Yeong;Hyun, Dong Yun;Kim, Dong Hwi
    • Korean Journal of Medicinal Crop Science
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    • v.28 no.1
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    • pp.9-20
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    • 2020
  • Background: Although a number of Panax ginseng cultivars have been developed by Korean researchers in recent years, there has been insufficient analysis of their beneficial properties. In this study, we sought to identify useful ginseng varieties as functional materials. Methods and Results: We evaluated effects of root extracts of 10 ginseng cultivars (Cheongsun; CS, Chunpoong; CP, Gopoong; GP, Gumpoong; GMP, K1, Sunhyang; SH, Sunone; SO, Sunpoong; SP, Sunun; SU and Yunpoong; YP) against the inhibitory effects of nitric oxide (NO) and reactive oxygen species (ROS) production in mouse brain microglial BV2 cells, as well as the binding of N-methyl-D-aspartate receptor (NMDAR), a marker related to memory. Ginsenosides, such as 20 (S)-protopanaxadiols (PPDs), including ginsenoside-Rb1, -Rb2, -Rb3, -Rc, -Rd, and - Rg3 and 20 (S)-protopanaxatriols (PPTs) including -Re, -Rg1, and -Rg2 were analyzed by HPLC. We observed that the cultivar GMP showed the highest inhibitory effect (60.8%) against NO production at 20 ㎍/㎖. Those cultivars showing the significantly highest inhibition effects against ROS at 20 ㎍/㎖ were K1 (57.3%), SP (54.5%), YP (53.1%), CP (51.7%), CS (50.9%) and SH (49.6%). At 50 ㎍/㎖, K1 showed the most potent inhibitory effect (51.2%) on NMDAR binding. The total phenol content of SH (1.89 mg/g) and K1 (1.73 mg/g) were higher than those of the other cultivars, whereas in terms of PD/PT ratios, the values of CP (0.98), K1 (1.05) and SO (1.05) were lower than those of the other cultivars. On the basis of correlation coefficient (0.7064) between NMDAR inhibition and ONOO- scavenging activity. Conclusions: The findings of this study indicate that the cultivars K1 and SH could be useful ginseng resources as functional materials with favorable cognition-improving and antioxidative properties.

Mechanisms Underlying the Inhibitory Effect of GS 283 in Various Smooth Muscles (GS 283의 평활근 억제 작용기전)

  • Kim, Si-Hwan;Lee, Young-Soo;Chong, Won-Seog;Chang, Ki-Churl
    • The Korean Journal of Pharmacology
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    • v.30 no.1
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    • pp.101-109
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    • 1994
  • Pharmacological characterization of GS 283, a tetrahydroisoquinoline derivative has been elucidated using rat thoracic aorta, guinea pig tenea coli and rabbit mesentery artery in vitro. GS 283 showed calcium antagonistic action in vascular smooth muscle, since high $K^+-induced$ contraction was concentration dependently inhibited. GS 283 also inhibited the contraction induced by ${\alpha}_1$ receptor activation. Vasodilating action of GS 283 was not modified by the propranolol, indicating that GS 283 has no ${\beta}$ receptor stimulatory action. Simultaneous measurement of intracellular calcium change and muscle tension indicated that the inhibitory effect of GS 283 was accompanied by the increase in tissue fluorescence. This increment was not due to fura 2 fluorescence but to endogenous pyridine nucleotide, suggesting that GS 283 has an effect to inhibit mitochondrial function. GS 283 had an inhibitory action on cyclic AMP and GMP-dependent phosphodiesterases from rat brain with Ki values of 2.5 and 6.7 mM. From these findings we concluded that GS 283 has multiple action such as the inhibition of cyclic nucleotide-dependent phosphodiesterases, blocking of calcium channel as well as inhibition of mitochondrial function which are responsible for vasodilatation.

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Effect of Lespedezea Cuneata on the Contraction of Rabbit Common Carotid Artery and Corpus Cavernosum (야관문(夜關門)이 토끼의 혈관과 음경해면체 수축에 미치는 영향)

  • Park, Sun Young;Kim, Ho Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.27 no.6
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    • pp.809-817
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    • 2013
  • The aim of this study was to evaluate the mechanism of vasodilation of Lespedezea cuneata(LC) in rabbit common carotid artery and cavernosal smooth muscle. LC relaxed arterial strips precontracted with norepinephrine and cavernosal strips precontracted with phenylephrine. The arterial relaxation effects of LC was endothelium-dependent. $N{\omega}$-nitro-L-arginine(L-NNA), NOS inhibitor, methylene blue(MB), cGMP inhibitor, indomethacin(IM), cyclo-oxygenase inhibitor and tetraethylammonium chloride(TEA), KCa-channel blocker attenuate the relaxation responses of LC in arterial strips. In $Ca^{2+}$-free krebs-ringer solution, pretreatment of LC extract significantly reduced the contraction induced by addition $Ca^{2+}$. L-NNA reduced LC extract-induced relaxation in cavernosal strips, but IM, TEA and MB didn't affect LC extract-induced relaxation. When LC extract was applicated on human umbilical vein endothelial cell, the nitric oxide concentration was increased. We conclude that in rabbit common carotid artery, LC may suppress influx of extra-cellular $Ca^{2+}$ through the release of endothelium derived relaxing factor including nitric oxide, prostacyclin, endothelium derived hyperpolarizing factor. And LC exerts a relaxing effect on corpus cavernosum through activating the NO.

Biochemical Characterization of the Interaction between Small Phosphoproteins and Transducin in Frog Photoreceptors

  • Suh, Kyong-Hoon
    • BMB Reports
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    • v.29 no.4
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    • pp.372-379
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    • 1996
  • Components I and II (CI&II) are major phosphoproteins in the frog rod outer segments (ROS) of retina, whose phosphorylation is light- and cyclic nucleotide-dependent. Although it was reported that CI & II could be chemically cross-linked to ${\beta}{\gamma}-subunit$ of transducin (${\beta}{\gamma}_t$), it was not clear whether CI&II physically interact with ${\beta}{\gamma}_t$, under native conditions. CI&II extracted by hypotonic washing fo ROS membranes showed an overlapped migration with ${\beta}{\gamma}_t$, in sucrose density gradient centrifugation. The elution profile of CI&II in the peripheral membrane fractions from gel filtration chromatography also overlapped that of ${\beta}{\gamma}_t$. These hydrodynamic parameters indicate that the native molecular state of CI&II in the peripheral membrane fraction appears to be within a complex, most likely with ${\beta}{\gamma}_t$. CI&II coeluted with ${\beta}{\gamma}_t$, showed no phosphorylation by endogenous kinase which phosphorylates a serine of CI&II in other fractions. The purified CI&II were not able to inhibit trypsin-activated cGMP-phosphodiesterase, and CI&II were not recognized by a monoclonal antibody against the ${\gamma}-subunit$ of transducin, indicating that CI&II are not y-subunit of PDE or transducin. Thus, it is likely that native CI&II, which undergo a light-dependent phosphorylation/dephosphorylation cycle, can associate with ${\beta}{\gamma}$, in frog photoreceptor membranes, and the complex formation has an inhibitory effect on the endogenous phosphorylation of CI&II.

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