• Title/Summary/Keyword: Guanosine-5'-monophosphate

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Attenuation of monocrotaline-induced pulmonary hypertension with DA-8159, a potent PDE 5 inhibitor

  • Ahn, Gook-Jun;Kang, Kyung-Koo;Sohn, Yong-Sung;Choi, Seu-Min;Kim, Ju-Mi;Kim, Dong-Hwan;Ahn, Byoung-Ok;Kim, Won-Bae
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.249.1-249.1
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    • 2002
  • This study was carried out to demonstrate the effects of oral administration of DA-8159. a selective phosphodiesterase 5 inhibitor. on development of pulmonary hypertension induced by monocrotaline (MCT). MCT-treated rats(60mg/kg) were divided into three groups and orally administered vehicle, 1 mg/kg or 5 mg/kgg of DA-8159 twice a day for 3 weeks. Increased right ventricular weights, medial wall thickening in pulmonary arteries. myocardial fibrosis, decrease of plasma cyclic guanosine monophosphate (cGMP) level and body weight gains were shown in MCT group. (omitted)

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Sildenafil Citrate Induces Migration of Mouse Aortic Endothelial Cells and Proteinase Secretion

  • Kim, Young-Il;Oh, In-Suk;Park, Seung-Moon;Kim, Hwan-Gyu
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.5
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    • pp.402-407
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    • 2006
  • Vascular endothelial cells release proteinases that degrade the extracellular matrix (ECM), thus enabling cell migration during angiogenesis and vasculogenesis. Sildenafil citrate stimulates the nitric oxide-cyclic guanosine monophosphate pathway through inhibition of phosphodiesterase type V (PDE5). In this report, we examined the mechanisms underlying sildenafil citrate-induced cell migration using cultured mouse aortic endothelial cells (MAECs). Sildenafil citrate induced migration and proteinase secretion by murine endothelial cells. Sildenafil citrate induced the secretion of matrix metalloproteinase-2 (MMP-2) and MMP-9, which is inhibited by $NF-{\kappa}B$ inhibitors. Sildenafil citrate also induced the secretion of plasmin, which is inhibited by PI 3'-kinase inhibitors. It is suggested that sildenafil citrate-induced migrating activity in endothelial cells may be accomplished by increased secretion of proteinases.

Modulation of $Ca^{2+}-Activated$ Potassium Channels by cGMP-Dependent Signal Transduction Mechanism in Cerebral Arterial Smooth Muscle Cell of the Rabbit

  • Han, Jin;Kim, Na-Ri;Lee, Kwang-Bok;Kim, Eui-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.4 no.6
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    • pp.445-453
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    • 2000
  • The present investigation tested the hypothesis that the activation of protein kinase G (PKG) leads to a phosphorylation of $Ca^{2+}-activated$ potassium channel $(K_{Ca}\;channel)$ and is involved in the activation of $K_{Ca}$ channel activity in cerebral arterial smooth muscle cells of the rabbit. Single-channel currents were recorded in cell-attached and inside-out patch configurations of patch-clamp techniques. Both molsidomine derivative 3-morpholinosydnonimine-N-ethylcarbamide $(SIN-1,\;50\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate $(8-pCPT-cGMP,\;100\;{\mu}M),$ a membrane-permeable analogue of cGMP, increased the $K_{Ca}$ channel activity in the cell-attached patch configuration, and the effect was removed upon washout of the drugs. In inside-out patches, single-channel current amplitude was not changed by SIN-1 and 8-pCPT-cGMP. Application of ATP $(100\;{\mu}M),$ cGMP $(100\;{\mu}M),$ ATP+cGMP $(100\;{\mu}M\;each),$ PKG $(5\;U/{\mu}l),$ ATP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l),$ or cGMP $(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ did not increase the channel activity. ATP $(100\;{\mu}M)+cGMP\;(100\;{\mu}M)+PKG\;(5\;U/{\mu}l)$ added directly to the intracellular phase of inside-out patches increased the channel activity with no changes in the conductance. The heat-inactivated PKG had no effect on the channel activity, and the effect of PKG was inhibited by 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer $(Rp-pCPT-cGMP,\;100\;{\mu}M),$ a potent inhibitor of PKG or protein phosphatase 2A (PP2A, 1 U/ml). In the presence of okadaic acid (OA, 5 nM), PP2A had no effect on the channel activity. The $K_{Ca}$ channel activity spontaneously decayed to the control level upon washout of ATP, cGMP and PKG, and this was prevented by OA (5 nM) in the medium. These results suggest that the PKG-mediated phosphorylations of $K_{Ca}$ channels, or some associated proteins in the membrane patch increase the activity of the $K_{Ca}$ channel, and the activation may be associated with the vasodilating action.

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Fatty acid profiles and flavour-related compounds of retorted Korean ginseng chicken soup (Samgyetang) affected by pre-treated black garlic extract

  • Barido, Farouq Heidar;Utama, Dicky Tri;Kim, Yeong Jong;Lee, Sung Ki
    • Animal Bioscience
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    • v.35 no.7
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    • pp.1080-1090
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    • 2022
  • Objective: This study aimed to characterize the effect of pre-treated black garlic (BG) extracts addition into retorted Korean ginseng chicken soup (Samgyetang) on the fatty acid composition and flavour-related indexes. Methods: Four different treatments; Samgyetang made with a 5% (w/w) addition of garlic (G), fresh BG (FBG), oven-dried BG (DBG), or encapsulated BG (EBG) extracts were developed and compared to negative control (NC) without any extract addition. Prepared samples were cooked via retorting at 121.1℃, 1.5 kgf/cm2 for 1 h. Results: The BG treated samples were higher in C18:3n3 and C18:2n6 fatty acids, with thrombogenic index was 18% to 20% lower than the NC. EBG yielded the highest umami-related nucleotides (5'-guanosine monophosphate and 5'-inosine monophosphate) and modified some free amino acid (alyne, phenylalanine and leucine) thus possessed the highest equivalent umami concentration among samples. Some individual aldehydes (pentanal, hexanal, and heptanal) were lower, while furans and volatile sulfur compounds were higher than the NC and G treatment group, indicating a potential suppression of unpleasant flavour alongwith the intensificiation of favourable flavour from the addition of BG extracts into retorted Samgyetang. Conclusion: Taken together, the synergistic results of this study indicate that incorportating suitable pre-treatment of BG extract could be of critical importance for the development of the retorted Samgyetang with improved flavour and functionalities.

Experimental Study of Patholobi Caulis on the Transient Cerebral Ischemia in Rats (계혈등(鷄血藤) 추출물이 뇌허혈에 미치는 실험적 연구)

  • Lee, Sang-Lok;Choi, Chan-Hun;Baek, Jin-Ung;Youn, Dae-Hwan;Jeong, Sang-Hun;Han, Ung;Jeong, Hyun-Woo;Kim, Gye-Yeop
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1127-1134
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    • 2007
  • The study was designed to investigate the mechanism of Patholoobi Caulis freeze dried powder (PCF) on the regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats and cytokines production ($IL-1{\beta}$, $TNF-{\alpha}$, IL-10, $TGF-{\beta}$) in cerebral ischemic rats. The results in normal rats were as follows ; Increase of PCF-induced rCBF was significantly inhibited by pretreatment with methylene blue (10 ${\mu}g/kg$, I.p.), an inhibitor of guanylate cyclase, and was inhibited by indomethacin (1 mg/kg, i.p.), an inhibitor of cyclooxygenase. Increase of PCF-induced MABP was decreased by pretreatment with methylene blue, but was increased by indomethacin. These results suggested that the mechanism of action PCF was mediated by cyclic 3',5'-guanosine monophosphate. The results in cerebral ischemic rats were as follows ; In cytokine production in serum from femoral arterial blood 1 hr after middle cerebral arterial occlusion, PCF (10 mg/kg. i.p.) significantly decreased $IL-1{\beta}$ and $TNF-{\alpha}$ production, and increased IL-10 production compared with control group. In cytokine production in serum from femoral arterial blood 1 hr 1 hr after reperfusion, PCF (10 mg/kg, i.p.) significantly decreased $IL-1{\beta}$ production, and incresed IL-10 production compared with control group. These results suggested that PCF was significantly and stably increased regional cerebral blood flow by inhibiting $IL-1{\beta}$ production, and by accelerating IL-10 production.

Increase of L-type Calcium Current by cGMP-dependent Protein Kinase Regulates in Rabbit Ventricular Myocytes

  • Han, Jin;Kim, Na-Ri;Kim, Eui-Yong;Ho, Won-Kyung;Earm, Yung-E;Kim, Han-Kyoun
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.6
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    • pp.733-742
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    • 1998
  • Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

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Effects of $\gamma$-Irradiation and Subsequent Storage on Amino Acids and Ribonucleotides of Biled-Dried Anchovy

  • Kwon, Joonh-Ho;Byun, Myung-Woo
    • Preventive Nutrition and Food Science
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    • v.1 no.1
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    • pp.16-22
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    • 1996
  • Amino acids and ribonucleotides were measured for boiled-dried anchovy to determine the effect of 5 kGy γ-irradiation on its quality stability during storage at ambient and cooling (5∼10℃) temperatures for 12 months in a laminated-film package(Polyethylene 10㎛). The anchovy samples contained about 55%(d.b) of total amino acids and about 1%(d.b) of free amino acids. Although there found a significant change(p<0.01) in the content of leucine and lysine immediately sfter irradiation, the overall content of toral amino acids was little changed in stored anchovy even six months after irradiation at cooling conditions. γ-Irradiation caused a significant reduction(p<0.01) in the total content of free amino acids, showing a similar tendency by storage conditions. However, the ribonucleotides. which were 12.00mg/g(d.b) in inosine-5'-monophosphate and 0.38mg/g(d.b) in guanosine-5'-monophospate, were resistant to 5kGy-irradiation. With the lapse of storage time, it was also shown that storage temperature was more influential than irradiation on the contents of amino acids and taste compounds of dried anchovy.

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Inhibitory Effect of Ginkgolide B on Platelet Aggregation in a cAMP- and cGMP-dependent Manner by Activated MMP-9

  • Cho, Hyun-Jeong;Nam, Kyung-Soo
    • BMB Reports
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    • v.40 no.5
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    • pp.678-683
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    • 2007
  • Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

Quality Improvement of Pork Loin by Dry Aging

  • Lee, Cheol Woo;Lee, Ju Ri;Kim, Min Kyu;Jo, Cheorun;Lee, Kyung Haeng;You, Insin;Jung, Samooel
    • Food Science of Animal Resources
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    • v.36 no.3
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    • pp.369-376
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    • 2016
  • This study aimed to investigate the effects of dry aging on the quality of pork loin. Longissimus lumborum muscles were dissected from the right half of five pork carcasses and were used as the control samples. The left halves of the carcasses were aged at 2±1℃ and a relative humidity of 80% for 40 d. The total aerobic bacteria count was similar between the control and dry-aged pork loin (p>0.05). Lactic-acid bacteria was absent in both the control and dry-aged pork loins. Dry-aged pork loin contained low moisture and high protein and ash compared to the controls (p<0.05). The pH was higher and cooking loss was lower in dry-aged pork loin compared to that in the control (p<0.05). Flavor related compounds, such as total free amino acid, hypoxanthine, and inosine of pork loin were higher in dry-aged pork loin; whereas, inosine 5'-monophosphate and guanosine 5'-monophosphate were low in dry-aged pork loin than control (p<0.05). There was no difference in carnosine and anserine content between dry-aged pork loin and the control (p>0.05). Dry-aged pork loin had lower hardness and shear force and received higher core in sensory evaluation than the control (p<0.05). According to the results, dry aging improved textural and sensorial quality of pork loin.

Studies on the Mechanical Activities of Rabbit Myometrium V. Effects of Acetylcholine, Oxytocin and Prostagla, din F2α on Cyclic Nucleotide Levels of Rabbit Whole Uterus (가토 척출 자궁근의 운동성에 관한 연구 V. Acetylcholine, PGF2α 및 Oxytocin의 자궁 수축기전에 관한 연구)

  • Lee, Chang-Eop;Kwun, Jong-Kuk;Lee, Joong-Sup;Yang, Il-Suk;Lee, Mun-Han
    • Korean Journal of Veterinary Research
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    • v.22 no.1
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    • pp.1-8
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    • 1982
  • The effect of acetylcholine, oxytocin and prostaglandin $F_{2{\alpha}}$ ($PGF_{2{\alpha}}$) on cyclic nucleotide levels in estrogen-primed rabbit whole uterus were studied in the presence and absence of 1-methyl-3-isobutyl xanthine (MIX), a phosphodiestrase inhibitor, and indomethacin, a prostagandin inhibitor. In the absence of MIX, acetylcholine increased guanosine 3', 5'-cyclic monophosphate (cGMP), but had no effect on adenosine 3', 5'-cyclic monophosphate (cAMP) levels. In contrast, oxytocin had no influence on cGMP, but decreased cAMP levels. $PGF_{2{\alpha}}$ increased cGMP and decreased cAMP levels. MIX increased both cAMP and cGMP levels. Oxytocin and $PGF_{2{\alpha}}$ further increased cGMP levels, indicating activation of guanylate cyclase activity. The ratio of cAMP/cGMP was decreased by uterine stinulants both in presence and absence of MIX. Indomethacin elevated cAMP and cGMP revels. The effects of uterine stimulants in the presence of indomethacin on cyclic nucleotide levels were varied from tissue to tisse. In general, oxytocin decreased cGMP and $PGF_{2{\alpha}}$ increased cAMP/cGMP levels, but the effects were statisically nonsignicficant. The cAMP/cGMP ratio was increased by uterine stimulant in the presence of indomethacin. In conclusion, uterine stimulants eased cAMP/cGMP ratio which indicates that the uterine stimulants have opposing effects on adenylate cyclase and guanylate cyclase activities. The endometrium plays a role in the regulation of cyclic nucleotide levels and uterine contraction by means of PG synthesis. Indomethacin has an unknown activities besides both of PG synthetase and phosphodiesterase inhibitions.

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