• Korean Journal of Veterinary Research
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• v.40 no.4
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• pp.691-699
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• 2000

We investigated the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on the contractile and electrical activity of the circular muscle of guinea pig gastric antrum by using intracellular microelectrode technique. The gastric antral circular muscle showed spontaneous phasic contraction and slow wave of membrane potential. Cys-NO ($0.001{\sim}10{\mu}M$) and SIN-1 ($0.001{\sim}100{\mu}M$) reduced not only the tonic and phasic contraction but also the amplitude of slow wave in a concentration dependent manner. NO donors were more potent to inhibit phasic contraction than to do slow wave. These inhibitory effects of NO donors were mimicked by the membrane permeable guanosine-3',5'-cyclic monophosphate (cGMP) analogue, 8-bromo-cyclic GMP (8-br-cGMP, $10{\sim}300{\mu}M$). The inhibitory effects of SIN-1 and Cys-NO were antagonized by the guanylate cyclase inhibitor, 1H[ [1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, $10{\mu}M$). These results suggest that the inhibitory effects of NO donors on the mechanical and electrical activity is mainly mediated by cGMP pathway.

• Journal of Ginseng Research
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• v.40 no.4
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• pp.334-343
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• 2016

Background: Progressed tissue culture techniques have allowed us to easily obtain mass products of tissue-cultured mountain ginseng over 100 yr old (TCMG-100). We investigated the effects of TCMG-100 extract on erectile function using in vitro and in vivo studies. Methods: To examine the relaxation effects and mechanisms of action of TCMG-100 on rabbit cavernosal strips evaluated in an organ bath. To investigate the long-term treatment effect of TCMG-100, 8-wk administration was performed. After administration of TCMG-100, intracavernosal pressure, cyclic guanosine monophosphate and nitric oxide (NO) levels of cavernosal tissue, serum testosterone level, histological observation of collagen fiber, endothelium, smooth muscle cell, and transforming growth factor-${\beta}1$ were investigated. Results: TCMG-100 extract displayed dose-dependent relaxation effects on precontracted rabbit corporal smooth muscle. The TCMG-100-induced relaxation was significantly reduced by removing the endothelium, and treatment with an NO synthase inhibitor or NO scavenger. Eight weeks of TCMG-100 administration increased intracavernosal pressure in a rat model. The levels of cyclic guanosine monophosphate and NO in the corpus callosum and serum testosterone level were also increased by TCMG-100 treatment. Furthermore, histological evaluation of collagen, smooth muscle, and endothelium showed increases in endothelium and smooth muscle, and a decrease in transforming growth factor-${\beta}1$ expression. Conclusion: These relaxation effects on corporal smooth muscle and increased erectile function suggest that TCMG-100 might be used as an alternative herbal medicine to improve erectile function.

• Archives of Pharmacal Research
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• v.19 no.3
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• pp.201-206
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• 1996

Nitric oxide (NO) is thought to be a second messenger involved in secretion. Upon stimulating pancreatic acinar cells with cholecystokinin-pancreozymin (CCK-PZ), NO formation has been shown to be associated with increased levels of cGMP (Seo et al., 1995). To elucidate the signaling pathway of VIP-induced enzyme secretion, we investigated the NO and cGMP synthesis steps as potential steps where two signal pathways triggered by CCK-PZ and VIP interact. The results obtained in this work provide evidence that increase in pancreatic enzyme secretion by treatment with VIP has no relationship with NOS activity and cGMP level. This conclusion was derived from the following findings that VIP treatment of rat pancreatic tissue increased amylase release as well as protein output in a dose- and time-dependent manner, whereas NOS activity and cGMP synthesis were not affected by VIP treatment as monitored by NOS activity assay and determining cGMP level, which was further confirmed by a NOS-inhibitor study. Consequently, CCK-PZ or VIP increases enzyme secretion in rat pancreatic tissue, but the two hormones are different in their mode of action. Together the results suggest that signaling pathway of VIP-induced enzyme secretion might either bypass the NO and cGMP synthesis steps or lie on a distinct pathway from CCK-PZ-induced pathway.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.219-231
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• 1995

Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.

• Journal of the Earthquake Engineering Society of Korea
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• v.6 no.4
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• pp.31-37
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• 2002

Recently a simplified design procedure as well as load transfer model for seismic steel moment connections with welded straight haunch have been proposed by Lee and Uang. Cyclic seismic testing was conducted to verify the proposed design procedure and to develop the details that will prevent the cracking at the haunch tip, where stress concentration was the highest. All the specimens thus designed effectively pushed plastic hinging away from the haunch tip and were able to develop satisfactory plastic rotation capacity of 0.04 radian with no fracture. A sloped edge combined with drilling a hole near the haunch tip or a pair of stiffeners(partially or fully) extended from the beam web successfully prevented the crack initiation at the haunch tip. The strut action of the haunch web, which had been predicted from the previous analytical study, was also experimentally identified through the strain gage readings.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.221-226
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• 2023

Proper activation and aggregation of platelets are necessary, but excessive or abnormal aggregation can lead to cardiovascular diseases such as stroke, thrombosis, and atherosclerosis. Therefore, identifying a substance that can regulate or inhibit platelet aggregation is important for preventing and treating these diseases. Several studies have shown that certain ginsenoside compounds in Panax ginseng can inhibit platelet aggregation. Among these compounds, Rk3 (G-Rk3) from Panax ginseng needs to be further explored in order to reveal the mechanisms of action during inhibition. G-Rk3 significantly increased amounts of cyclic adenosine monophosphate (cAMP) and led to significant phosphorylation of cAMP-dependent kinase substrates vasodilator-stimulated phosphoprotein and inositol 1,4,5-trisphosphate receptor. Furthermore, the effect of G-Rk3 extended to the inhibition of PI3K/Akt phosphorylation resulting in the reduced secretion of intracellular granules. Ultimately, G-Rk3 effectively inhibited platelet aggregation. Therefore, we suggest G-Rk3's potential as a prophylactic or therapeutic agent for cardiovascular diseases caused by faulty platelet aggregation.

• The Korean Journal of Pharmacology
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• v.18 no.2
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• pp.15-25
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• 1982

It was undertake to investigate the factors involved in the micro thrombus formation in the plasma from the patients with cerebrovascular disease(CVD) and the in vitro actions of sodium nitroprusside on the platelet aggregate formation. 1) The microthrombus formation in the plasma from CVD was significantly enhanced, in comparison with that from the healthy volunteers. 2) Both lipid peroxide and cathepsin D in the plasma from CVD were higher than those levels from the healthy volunteers. 3) Whereas the platelets from healthy individuals showed less aggregation activity in response to ADP in the second phase those from CVD revealed the enhanced aggregating response to ADP. 4) When the bovine basilar artery, rabbit aorta and human umbilical artery were pretreated with $K^+-free$ PSS, ouabain, 13-hydroperoxylinoleic acid(13-HPLA) and cadmium they markedly enhanced the platelet aggregability respectively. 5) Platelet aggregation induced by $K^+-free$ PSS-treated bovine basilar artery was decreased by sodium nitroprusside in a dose-dependent manner, but not by either hydralazine. 6) Both dibutyryl cyclic AMP and 8-bromo cyclic GMP had the inhibitory action on the platelet aggregation. However, the latter had more prominent action than former. The antiaggregating effect by sodium nitroprusside was antagonized by pretreatment with methylene blue, but not by hemoglobin. These results provide the evidences for the therapeutic use of sodium nitroprusside in the emergency of cerebrovascular disease and in remains the further study of the clinical therapy with it.

• Korean Journal of Veterinary Research
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• v.45 no.4
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• pp.507-515
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• 2005

Melatonin, the principal hormone of the vertebral pineal gland, participates in the regulation of cardiovascular system in vitro and in vivo. However, the effects of melatonin on vascular tissues are still vague. The aim of this study was to assess the relationship between phospholipase C (PLC) and nitric oxide synthase (NOS)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling cascade in the relaxatory action of melatonin in isolated rat aorta. Melatonin induced a concentration-dependent relaxation in phenylephrine (PE)- and KCl-precontracted endothelium intact (+E) aortic rings. In KCl-precontracted +E aortic rings, the melatonin-induced vasorelaxation was not inhibited by endothelium removal or by pretreatment with NOS inhibitors, L-$N^G$-nitor-arginine (L-NNA) and L-$N^G$-nitor-arginine methyl ester (L-NAME), guanylate cyclase (GC) inhibitors, methylene blue (MB) and 1H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one (ODQ). In PE-precontracted +E aortic rings, the melatonin-induced vasorelaxation was inhibited by endothelium removal or by pretreatment with L-NNA, L-NAME, MB, ODQ and 2-nitro-4-carboxyphenyl-n,n-diphenylcarbamate (NCDC). Moreover, in without endothelium (-E) aortic rings and in the presence of L-NNA, L-NAME, MB and ODQ in +E aortic rings, the melatonin-induced residual relaxations and residual contractile responses to PE were not affected by NCDC, a PLC inhibitor. It is concluded that melatonin can evoke vasorelaxation due to inhibition of PLC pathway through the protein kinase G activation of endothelial NOS/cGMP signaling cascade.

• The Journal of Korean Obstetrics and Gynecology
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• v.18 no.4
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• pp.72-84
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• 2005

Purpose : This study was carried out to investigate the relaxational response to the water extract of Sobokchukeo-Tang(SCT) in isolated uterine muscle in rats. Methods : Segments of uterine muscle obtained from female rats immediately after delivery were mounted in organ baths superfused on a polygraph. The effects of SCT on the tension of potassium induced contracture were studied in rat uterine smooth muscles. All experiments were performed in Krebs-Henseit solution which was aerated with 100% oxygen and kept at $37^{\circ}C$. Results : KCI did not produce contraction in calcium-free solution, but $CaCl_2$ induced concentration-dependent contraction after depolarizing with KCI. SCT inhibited the tonic contraction of uterine muscle as dose dependent manner. And when SCT was pretreated in calcium-free medium, it showed more powerful relaxational effect. The effect of 10mg/ml concentration of SCT was equal to that of 9nM and 70nM of nifedipine and verapamil and the relaxational effect of SCT on rat uterine muscle can be assumed to be concerned with the action of cyclic AMP. But the action mechanism of relaxation on the rat uterine muscles were concerned with the calcium channel. Conclusion : From this study we could suggest that the relaxtional effect of SCT on uterine muscle be available to preventing and curing dysmenorrhea.

• Bulletin of the Korean Chemical Society
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• v.33 no.4
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• pp.1135-1140
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• 2012

An electrochromatographic microchip with carboxyl-group-derivatized mono-disperse silica packing was prepared from the corresponding colloidal silica solution by utilizing capillary action and self-assembly behavior. The silica beads in water were primed by the capillary action toward the ends of cross-patterned microchannel on a cyclic olefinic copolymer (COC) substrate. Slow evaporation of water at the front of packing promoted the self-assembled packing of the beads. After thermally binding a cover plate on the chip substrate, reservoirs for sample solutions were fabricated at the ends of the microchannel. The packing at the entrances of the microchannel was silver coated to fix utilizing an electroless silver-plating technique to prevent the erosion of the packed structure caused by the sudden switching of a high voltage DC power source. The electrochromatographic behavior of the microchip was explored and compared to that of the microchip with bare silica packing in basic borate buffer. Electrophoretic migration of Rhodamine B was dominant in the microchip with the carboxyl-derivatized silica packing that resulted in a migration approximated twice as fast, while the reversible adsorption was dominant in the bare silica-packed microchip. Not only the faster migration rates of the negatively charged FITC-derivatives of amino acids but also the different migration due to the charge interaction at the packing surface were observed. The electrochromatographic characteristics were studied in detail and compared with those of the bare silica packed microchip in terms of the packing material, the separation potential, pH of the running buffer, and also the separation channel length.