Protective Mechanism of Nitric Oxide and Mucus against Ischemia/ Reperfusion-Induced Gastric Mucosal Injury

Hyeyoung,Kim,Kwangsoo,Nam,Kyung,Hwan,Kim 대한생리학회-대한약리학회 1998 The Korean Journal of Physiology & Pharmacology Vol.2 No.4

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<P> This study investigated the role of nitric oxide on the oxidative damage in gastric mucosa of rats which received ischemia/reperfusion and its relation to mucus. Nitric oxide synthesis modulators such as L-arginine and N<SUP>G</SUP>-nitro-L-arginine methyl ester, and sodium nitroprusside, a nitric oxide donor, were injected intraperitoneally to the rats 30 min prior to ischemia/reperfusion which was induced by clamping the celiac artery and the superior mesenteric artery for 30 min and reperfusion for 1 h. Lipid peroxide production, the contents of glutathione and mucus, and glutathione peroxidase activities of gastric mucosa were determined. Histological observation of gastric mucosa was performed by using hematoxylin-eosin staining and scanning electron microscopy. The result showed that ischemia/reperfusion increased lipid peroxide production and decreased the contents of glutathione and mucus as well as glutathione peroxidase activities of gastric mucosa. Ischemia/reperfusion induced gastric erosion and gross epithelial disruption of gastric mucosa. Pretreatment of L-arginine, a substrate for nitric oxide synthase, and sodium nitroprusside prevented ischemia/reperfusion-induced alterations of gastric mucosa. However, N<SUP>G</SUP>-nitro- L- arginine methyl ester, a nitric oxide synthase inhibitor, deteriorated oxidative damage induced by ischemia/reperfusion. In conclusion, nitric oxide has an antioxidant defensive role on gastric mucosa by maintaining mucus, glutathione, and glutathione peroxidase of gastric mucosa.

The Effects of Eupatilin (Stillen^Ⓡ) on Motility of Human Lower Gastrointestinal Tracts

Seung-Bum,Ryoo,Heung-Kwon,Oh,Sung,A,Yu,Sang,Hui,Moon,Eun,Kyung,Choe,Tae,Young,Oh,Kyu,Joo,Park 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.5

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Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen^Ⓡ) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer s bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen^Ⓡ) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

Chronic Non-Social Stress Affects Depressive Behaviors But Not Anxiety in Mice

Sang,Ho,Yoon,Byung-Hak,Kim,Sang-Kyu,Ye,Myoung-Hwan,Kim 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.3

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The etiology of most psychiatric disorders is still incompletely understood. However, growing evidence suggests that stress is a potent environmental risk factor for depression and anxiety. In rodents, various stress paradigms have been developed, but psychosocial stress paradigms have received more attention than non-social stress paradigms because psychosocial stress is more prevalent in humans. Interestingly, some recent studies suggest that chronic psychosocial stress and social isolation affects mainly anxiety-related behaviors in mice. However, it is unclear whether chronic non-social stress induces both depression- and anxiety-related phenotypes or induces one specific phenotype in mice. In the present study, we examined the behavioral consequences of three chronic non-social stress paradigms: chronic predictable (restraint) stress (CPS), chronic unpredictable stress (CUS), and repeated corticosterone-HBC complex injection (RCI). Each of the three paradigms induced mild to severe depression/despair-like behaviors in mice and resulted in increased immobility in a tail suspension test. However, anxiety-related phenotypes, thigmotaxis and explorative behaviors, were not changed by the three paradigms. These results suggest that depression- and anxiety-related phenotypes can be dissociated in mouse stress models and that social and non-social stressors might affect brain circuits and behaviors differently.

Ginger and Its Pungent Constituents Non-Competitively Inhibit Serotonin Currents on Visceral Afferent Neurons

Zhenhua,Jin,Goeun,Lee,Sojin,Kim,Cheung-Seog,Park,Yong,Seek,Park,Young-Ho,Jin 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.2

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Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy−induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug−induced emesis. Ginger-mediated antiemetic effect has been attri-buted to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concen-tration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT−evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT−evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT₃ receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT−induced emetic signal transmission in vagal afferent neurons.

Bcl-2 Knockdown Accelerates T Cell Receptor-Triggered Activation-Induced Cell Death in Jurkat T Cells

Yun-Jung,Lee,Tae,Joon,Won,Kyeong,Eun,Hyung,Mi,Ji,Lee,Young-hye,Moon,Ik,Hee,Lee,Byung,Sung,Go,Kwang,Woo,Hwang 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

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Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expre-ssion. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed B

Reversal of Cisplatin Resistance by Epigallocatechin Gallate Is Mediated by Downregulation of Axl and Tyro 3 Expression in Human Lung Cancer Cells

Kyung-Chan,Kim,ChuHee,Lee 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

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Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigal-locatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

Transient Receptor Potential C4/5 Like Channel Is Involved in Stretch-Induced Spontaneous Uterine Contraction of Pregnant Rat

Seungsoo,Chung,Young-Hwan,Kim,Ji-Hyun,Joeng,Duck-Sun,Ahn 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.6

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Spontaneous myometrial contraction (SMC) in pregnant uterus is greatly related with gestational age and growing in frequency and amplitude toward the end of gestation to initiate labor. But, an accurate mechanism has not been elucidated. In human and rat uterus, all TRPCs except TRPC2 are expressed in pregnant myometrium and among them, TRPC4 are predominant throughout gestation, suggesting a possible role in regulation of SMC. Therefore, we investigated whether the TRP channel may be involved SMC evoked by mechanical stretch in pregnant myometrial strips of rat using isometric tension measurement and patch-clamp technique. In the present results, hypoosmotic cell swelling activated a potent outward rectifying current in G protein-dependent manner in rat pregnant myocyte. The current was significantly potentiated by 1μM lanthanides (a potent TRPC4/5 stimulator) and suppressed by 10μM 2-APB (TRPC4-7 inhibitor). In addition, in isometric tension experiment, SMC which was evoked by passive stretch was greatly potentiated by lanthanide (1μM) and suppressed by 2-APB (10μM), suggesting a possible involvement of TRPC4/5 channel in regulation of SMC in pregnant myometrium. These results provide a possible cellular mechanism for regulation of SMC during pregnancy and provide basic information for developing a new agent for treatment of premature labor.

DehydroevodiamineㆍHCl Improves Stress-Induced Memory Impairments and Depression Like Behavior in Rats

Hee,Jin,Kim.*,Ki,Young,Shin.*,Keun-A,Chang,Sangzin,Ahn,Hee,Soon,Choi,Hye-Sun,Kim,Yoo-Hun,Suh 대한생리학회-대한약리학회 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.1

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DehydroevodiamineㆍHCl (DHED) has been reported to prevent memory impairment and neuronal cell loss in a rat model with cognitive disturbance. We investigated the effect of DHED on memory impairment and behavioral abnormality caused by stress. We demonstrated that DHED can improve stress-induced memory impairments and depression-like behaviors by using open-field test, Y-maze test and forced swimming test. DHED treatment significantly recovered the decreases in the levels of neural cell adhesion molecule (NCAM) proteins caused by stress and the decreases in cell viability. Our results suggested that DHED is a potential drug candidate for neuronal death, memory impair-ment and depression induced by stress.

Disappearance of Hypoxic Pulmonary Vasoconstriction and O<SUB>2</SUB>-Sen-sitive Nonselective Cationic Current in Arterial Myocytes of Rats Under Ambient Hypoxia

Hae,Young,Yoo,Sung,Joon,Kim 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.5

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Acute hypoxia induces contraction of pulmonary artery (PA) to protect ventilation/perfusion mismatch in lungs. As for the cellular mechanism of hypoxic pulmonary vasoconstriction (HPV), hypoxic inhibition of voltage-gated K<SUP>+</SUP> channel (Kv) in PA smooth muscle cell (PASMC) has been suggested. In addition, our recent study showed that thromboxane A<SUB>2</SUB> (TXA<SUB>2</SUB>) and hypoxia-activated nonselective cation channel (I<SUB>NSC</SUB>) is also essential for HPV. However, it is not well understood whether HPV is maintained in the animals exposed to ambient hypoxia for two days (2d<SUB>-</SUB>H). Specifically, the associated elec-trophysiological changes in PASMCs have not been studied. Here we investigate the effects of 2d<SUB>-</SUB>H on HPV in isolated ventilated/perfused lungs (V/P lungs) from rats. HPV was almost abolished without structural remodeling of PA in 2d<SUB>-</SUB>H rats, and the lost HPV was not recovered by Kv inhibitor, 4-aminopyridine. Patch clamp study showed that the hypoxic inhibition of Kv current in PASMC was similar between 2d<SUB>-</SUB>H and control. In contrast, hypoxia and TXA<SUB>2</SUB>-activated I<SUB>NSC</SUB> was not observed in PASMCs of 2d<SUB>-</SUB>H. From above results, it is suggested that the decreased I<SUB>NSC</SUB> might be the primary functional cause of HPV disappearance in the relatively early period (2 d) of hypoxia.

Effects of Vitamin D on Blood Pressure and Endothelial Function

Bokyung,Min 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.5

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Vitamin D deficiency is prevalent, primarily due to limited sun exposure, which may be observed in urban areas, or as a result of modern lifestyles. Common myths about vitamin D persist, including that it is mostly obtained from the diet and is only essential for bone and mineral homeostasis. Nonetheless, advances in biomedical science suggest that vitamin D is a hormone that is integral to numerous physiologic functions in most cells and tissues. Therefore, abnormal vitamin D levels may contribute to health disturbances. A number of recent reports on potential associations between vitamin D deficiency and cardiovascular disease have highlighted its role in this system. A focus over the previous decade has been to better understand the mechanisms behind vitamin D regulation and the pathophysiology associated with suboptimal vitamin D levels. Vitamin D deficiency is highly associated with the incidence of cardiovascular diseases, even when considering other well-known risk factors. In this process, the renin-angiotensin system is disrupted, and hypertension and endothelial dys-function contribute to the risk of cardiovascular disease. Likewise, clinical outcomes upon the normalization of vitamin D levels have been investigated in different patient populations. It makes sense that vitamin D supplementation to improve vitamin D status among vitamin D-deficient indi-viduals could be useful without requiring a sudden lifestyle change. This manuscript provides a brief overview of vitamin D metabolism and the vitamin D receptor. It also summarizes the current clinical research relating to vitamin D supplementation and its effects on hypertension and endothelial dysfunction in cardiovascular medicine.