• The Korean Journal of Physiology and Pharmacology
• /
• 제7권2호
• /
• pp.53-57
• /
• 2003

The glutamate receptors (GluRs) are key receptors for modulatory synaptic events in the central nervous system. It has been reported that glutamate increases the intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) and induces cytotoxicity. In the present study, we investigated whether the glutamate-induced $[Ca^{2+}]_i$ increase was associated with the activation of ionotropic (iGluR) and metabotropic GluRs (mGluR) in substantia gelatinosa neurons, using spinal cord slice of juvenile rats (10${\sim}21 day). $[Ca^{2+}]_i$ was measured using conventional imaging techniques, which was combined with whole-cell patch clamp recording by incorporating fura-2 in the patch pipette. At physiological concentration of extracellular $Ca^{2+}$, the inward current and $[Ca^{2+}]_i$ increase were induced by membrane depolarization and application of glutamate. Dose-response relationship with glutamate was observed in both $Ca^{2+}$ signal and inward current. The glutamate-induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV was blocked by CNQX, an AMPA receptor blocker, but not by AP-5, a NMDA receptor blocker. The glutamate-induced $[Ca^{2+}]_i$ increase in $Ca^{2+}$ free condition was not affected by iGluR blockers. A selective mGluR (group I) agonist, RS-3,5-dihydroxyphenylglycine (DHPG), induced $[Ca^{2+}]_i$ increase at holding potential of -70 mV in SG neurons. These findings suggest that the glutamate-induced $[Ca^{2+}]_i$ increase is associated with AMPA-sensitive iGluR and group I mGluR in SG neurons of rats.

• 생물정신의학
• /
• 제5권1호
• /
• pp.114-121
• /
• 1998

Bethanechol, a cholinergic agonist, has been recommended for the management of peripheral anticholinergic side effects during the treatment of antipsychotic medications. But there have been few studies which have evaluated the drug interactions of antipsychotics and bethanechol, even the treatment effects of bethanechol on anticholinergic side effects. So the authors have evaluated whether psychopathology and plasma haloperidol and reduced haloperidol concentrations are significantly changed or not when bethanechol was administrated with maintained doses of haloperidol and other coadministrated drugs(such a benztropine). Also we have evaluated the abating effects of bethanechol on anticholinergic side effects during the treatment with haloperidol. Fifteen schizophrenics with higher than 5 of total score of anticholinergic side effects of 'Rating scale for side effect' were assigned to two groups, and bethanechol 30mg/day and 60mg/day were applied on each group for 4 weeks. The daily haloperidol dosages were fixed before 2 weeks of study. We assessed anticholinergic side effects by 'Rating scale for side effect' and psychopathology by BPRS, and plasma haloperidol and reduced haloperidol concentrations by HPLC at baseline, 2nd week and 4th week. The results were as followed, 1) there was no significant change of plasma haloperidol and reduced haloperidol concentration, 2) at baseline, the dosage of haloperidol showed significant correlation with the total score of anticholinergic side effect, but not at 2nd week and 4th week, 3) in 60mg/day group, dry mouth and the total score of anticholinergic side effects were significantly improved, but not in 30mg/day group, 4) there was no significant change of BPRS except withdrawal at 2nd week. These results suggest that coadministration of bethanechol influenced neither on psychopathology nor on plasma haloperidol and reduced haloperidol concentrations and that improved dry mouth and total score of anticholinergic side effects at 60mg/day.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권7호
• /
• pp.3131-3138
• /
• 2016

Several studies have addressed the possible role of hepatitis C virus genotype-4 (HCV GT4) in apoptosis. However, this still not fully understood. In the current study a re-constructed clone of E1/E2 polyprotein region of the HCV GT4 was transfected into the Huh7 cell line and a human apoptotic PCR array of 84 genes was used to investigate its possible significance for apoptosis. Out of the 84 genes, only 35 showed significant differential expression, 12 genes being up-regulated and 23 down-regulated. The highest-up regulated genes were APAF1 (apoptotic peptidase-activating factor 1), BID (BH3 interacting domain death agonist) and BCL 10 (B-cell CLL/lymphoma protein 10) with fold regulation of 33.2, 30.1 and 18.9, respectively. The most down-regulated were FAS (TNF receptor super family), TNFRSF10B (tumor necrosis factor receptor super-family member 10b) and FADD (FAS-associated death domain) with fold regulation of -30.2, -27.7 and -14.9, respectively. These results suggest that the E1/E2 proteins may be involved in HCV-induced pathogenesis by modulating apoptosis through the induction of the intrinsic apoptosis pathway and disruption of the BCL2 gene family.

• 한국생물물리학회:학술대회논문집
• /
• 한국생물물리학회 2003년도 정기총회 및 학술발표회
• /
• pp.51-51
• /
• 2003

The medicinal plant Cimicifuga Racemosa (Black cohosh) has been used to treat many kinds of neuronal and menopausal symptoms, such as arthritis, menopausal depression, nerve pain, etc. Here, we examined the effect of Cimicifugoside (CF), one of triterpene glycosides which have been known as pharmacologically active ingredients of C. Racemosa, on nicotinic acetylcholine receptor (nAChR)-mediated catecholamine (CA) secretion in bovine adrenal chromaffin cell. Cimicifugoside inhibited calcium increase induced by 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nAChR agonist with a half maximal inhibitory concentration (IC50) of 18${\pm}$2${\mu}$M. In contrast, cimicifugoside did not affect the calcium increases evoked by high K$\^$+/, veratridine, and bradykinin. The DMPP-induced sodium increase was also inhibited by cimicifugoside with IC50 of 2${\pm}$0.3${\mu}$M, suggesting that the activity of nAChRs is inhibited by cimicifugoside. Cimicifugoside did not effect on the KCl-induced secretion but markedly inhibited the DMPP-induced catecholamine secretion which was monitored by carbon-fiber amperometry in real time, and by high performance liquid chromatography (HPLC) through electrochemical detection. The results suggest that cimicifugoside selectively inhibits nAChR-mediated response in bovine chromaffin cells.

• Journal of Ginseng Research
• /
• 제45권6호
• /
• pp.683-694
• /
• 2021

Background: Ginsenoside Rg1 (Rg1) has been well documented to be effective against various cardiovascular disease. The aim of this study is to evaluate the effect of Rg1 on mechanical stress-induced cardiac injury and its possible mechanism with a focus on the calcium sensing receptor (CaSR) signaling pathway. Methods: Mechanical stress was implemented on rats through abdominal aortic constriction (AAC) procedure and on cardiomyocytes and cardiac fibroblasts by mechanical stretching with Bioflex Collagen I plates. The effects of Rg1 on cell hypertrophy, fibrosis, cardiac function, [Ca²⁺]_i, and the expression of CaSR and calcineurin (CaN) were assayed both on rat and cellular level. Results: Rg1 alleviated cardiac hypertrophy and fibrosis, and improved cardiac decompensation induced by AAC in rat myocardial tissue and cultured cardiomyocytes and cardiac fibroblasts. Importantly, Rg1 treatment inhibited CaSR expression and increase of [Ca²⁺]_i, which similar to the CaSR inhibitor NPS2143. In addition, Rg1 treatment inhibited CaN and TGF-b1 pathways activation. Mechanistic analysis showed that the CaSR agonist GdCl₃ could not further increase the [Ca²⁺]_i and CaN pathway related protein expression induced by mechanical stretching in cultured cardiomyocytes. CsA, an inhibitor of CaN, inhibited cardiac hypertrophy, cardiac fibrosis, [Ca²⁺]_i and CaN signaling but had no effect on CaSR expression. Conclusion: The activation of CaN pathway and the increase of [Ca²⁺]_i mediated by CaSR are involved in cardiac hypertrophy and fibrosis, that may be the target of cardioprotection of Rg1 against myocardial injury.

• Clinical and Experimental Reproductive Medicine
• /
• 제28권3호
• /
• pp.225-233
• /
• 2001

Objective : To evaluate the efficacy of low-dose aspirin on IVF outcome and endometrium in patients undergoing IVF-ET. Materials and Methods : From February, 2001 to Jun, 2001, 60 infertile patients were randomly divided into study group (28 cycles) and control group (32 cycles). The study group received a daily oral dose of 25 mg of aspirin for at least 2 weeks from first visiting day. Controlled ovarian hyperstimulation was initiated in all patients with the GnRH agonist starting in the midluteal phase of the previous cycle. Results: There were no significant differences in age of the patients, basal serum E2, LH, FSH level and endometrial thickness among two groups. There were no statistically significant differences between the study group and the control group respectively in dosage ($26.5{\pm}4.8$ vs $26.2{\pm}5.3$ amples) and duration ($10.4{\pm}4.2$ vs $9.8{\pm}5.3$ days) of gonadotropin administration, serum E2 level on the hCG administration day ($1823{\pm}342$ vs $1854{\pm}543$), LH ($14.5{\pm}2.7$ vs $14.8{\pm}3.1$), FSH ($16.7{\pm}3.4$ vs $18.3{\pm}4.7$), the number of follicles > 15 mm ($13.2{\pm}6.3$ vs $12.8{\pm}5.9$), the number of oocytes retrieved ($9.2{\pm}2.4$ vs $8.4{\pm}1.7$), the number of embryos transferred ($4.7{\pm}2.0$ vs $4.7{\pm}2.0$), fertilization rate (68.4% vs 64.5%), implantation rate (21.3% vs 17.6%), and clinical pregnancy rate (28.4% vs 26.2%). The endometrial thickness and the percentage of endometrial trilaminar pattern on hCG day were significantly higher in study group than control group ($12.9{\pm}3.7mm$ vs $10.4{\pm}2.8mm$, 78.3% vs 64.5%). Conclusion: Many reports suggest that low-dose aspirin improve ovarian response, implantation rate, fertilization rate, implantation rate, and pregnancy rate by increasing the blood flow, but we couldn't prove the significant effect of low-dose aspirin on the IVF outcome except on endometrium. This may be affected by dose of aspirin, duration, and number of patients studied. This trial is small, so our results highlight the need for a large randomized controlled trial to identify the effect of low-dose as pirin on IVF-ET outcome.

• 한국식품영양과학회지
• /
• 제26권1호
• /
• pp.37-44
• /
• 1997

본 실험은 시중에서 판매하는 소시지를 전자렌지(micro-waving), 가스오븐(gas-broiling), 튀김 (frying)으로 조리한 다음, 냉장.저장하였다가 3일째, 6일째에 각 각 재가열하여 관능검사와 조직감 측정을 하였다. 이를 통하여 조리 방법, 냉장.저장 후 재가열에 따른 조직 특성에 대해 연구하여 다음과 같은 결론을 보고하는 바이다. 관능검사결과를 조리 방법 별로 살펴보면 조리 하지 않은 상태의 소시지가 촉촉한 정도, 경도에서 높은 수치를 나타내었으며, 짠맛의 정도는 재가열함에 따라 수치가 높아졌다. 저작성은 전자렌지 조리에서 높은 수치를 보였으나 두 제조회사 제품이 다른 양상을 보였다. 뒷맛은 가스오븐 조리에서 가장 높게 나타났고, 조리하지 않은 상태의 소시지가 뒷맛이 가장 약함을 보였다. 산패취는 다른 조리방법에 비하여 튀김 조리에서 유의하게 높게 나타났다. 조리하여 냉장 저장 한 후 3일째, 6일째 재가열했을 때, 저장 기간이 길어짐 에 따라 경도, 짠맛의 정도, 산패취, 뒷맛의 수치는 증가함을 보였으나 촉촉한 정도, 저작성은 감소함을 보였다. 전반적인 기호도는 전자렌지와 가스오븐으로 조리하여 냉장.저장한 후 3일째 재가열했을 때가 가장 높은 수치를 나타내었다. 기계적인 분석을 하였을 때 튀김조리에서 경도, 뭉침성, 씹힘성이 높은 수치를 나타냈으며, 응집성과 탄력성에서는 조리방법 별로 유의한 차이는 나타내지 않았다. 조리하여 냉장.저장한 후 재가열할 때에는 3일째, 6일째 재가열할수록 경도, 응집성, 탄력성, 뭉침성, 씹힘성이 증가하는 경향을 보였다. 경도, 응집성, 뭉침성, 씹힘성은 가스오븐으로 조리하여 냉장 저장한 후 3일째에 재가열한 소시지에서 유의하게 높았다.우(각각 20.0%), 땅콩 및 콩(각각 16.7%) 등의 순이었다. 연령 대별로는 10대 이하에서는 우유, 20대~30대에서는 복숭아, 40대 이상에서는 돼지고기가 많이 나타났다.ing of [sub 3/H]SR95531 to GABA receptor. Butanol fraction of G. elata significantly diminished the pentylenetetrazole-induced lethality of mice. From these results, it can be concluded that substance or substances with neurochemical properties characteri- stic of a benzodiazepine receptor agonist may be important components, and contribute to the anticonvulsant property of G. elata.clooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
• /
• pp.170-170
• /
• 1998

In order to discover new types of 5-hydroxytryptamine antagonists, we have devoted our attention to investigating naturally occurring compounds having anti-5HT activity in vitro. Recently, ${\gamma}$-mangostin [1,3,6,7-tetrahydroxy-2,8-bis(3-methyl-2-bytenyl)-9H-xanthen-9-one] from the fruit hull of Garcinia mangostana Linn has been shown to be a selective antagonist for 5-hydroxytryptamine$_{2A}$ receptors in smooth muscle and platelets. It is of interesting that y-mangostin which does not have a nitrogen atom, possesses marked 5-$HT_{2A}$ receptor blocking activity. The present study was undertaken to investigate the effects of ${\gamma}$-mangostin on central 5-HT receptors by using animal behavioural models. Intracerebronventricular injection of ${\gamma}$-mangostin (10-40n mol/mouse) inhibited 5-fluoro-${\alpha}$-methyltryptamin (5-FMT) (45 mg kg$^{-1}$, i.p.)-induced head-twitch response in mice in the presence or absence of citalopram (5-HT-uptake inhibitor). Neither the 5-FMT- nor the 8-hydroxy-2-( di-n-propylamino )tetralin (5-HT$_{1A}$-agonist)-induced 5-HT syndrome (head weaving and hindlimb abduction) was affected by ${\gamma}$-mangostin. The locomotor activity stimulated by 5-FMT through the activation of at-adrenoceptors did not alter in the presence of ${\gamma}$-mangostin. 5-HT-induced inositol phosphates accumulation in mouse brain slices was abolished by ketanserin. ${\gamma}$-Mangostin caused a concentration-dependent inhibition of the inositol phosphates accumulation and the binding of [$^3H$]-spiperone, a specific 5-$HT_{2A}$ receptor antagonist, to mouse brain membranes. Kinetic analysis of the [$^H3$]-spiperone binding revealed that ${\gamma}$-mangostin increased the $_{d}$ value without affecting the $B_{max}$ value, indicating the mode of the competitive nature of the inhibition by ${\gamma}$-mangostin. These results suggest that ${\gamma}$-mangostin inhibits 5-FMT-induced head-twitch response in mice by blocking 5-$HT_{2A}$ receptors not by blocking the release of 5-HT from the central neurone. ${\gamma}$-Mangostin is a promising 5-$HT_{2A}$ receptors antagonist in the central nervous system.m.

• The Korean Journal of Physiology and Pharmacology
• /
• 제18권4호
• /
• pp.297-305
• /
• 2014

Flavonoids have an ability to suppress various ion channels. We determined whether one of flavonoids, cyanidin-3-glucoside, affects adenosine 5'-triphosphate (ATP)-induced calcium signaling using digital imaging methods for intracellular free $Ca^{2+}$ concentration ([$Ca^{2+}$]i), reactive oxygen species (ROS) and mitochondrial membrane potential in PC12 cells. Treatment with ATP ($100{\mu}M$) for 90 sec induced [$Ca^{2+}$]i increases in PC12 cells. Pretreatment with cyanidin-3-glucoside ($1{\mu}g/ml$ to $100{\mu}g/ml$) for 30 min inhibited the ATP-induced [$Ca^{2+}$]i increases in a concentration-dependent manner ($IC_{50}=15.3{\mu}g/ml$). Pretreatment with cyanidin-3-glucoside ($15{\mu}g/ml$) for 30 min significantly inhibited the ATP-induced [$Ca^{2+}$]i responses following removal of extracellular $Ca^{2+}$ or depletion of intracellular [$Ca^{2+}$]i stores. Cyanidin-3-glucoside also significantly inhibited the relatively specific P2X2 receptor agonist 2-MeSATP-induced [$Ca^{2+}$]i responses. Cyanidin-3-glucoside significantly inhibited the thapsigargin or ATP-induced store-operated calcium entry. Cyanidin-3-glucoside significantly inhibited the ATP-induced [$Ca^{2+}$]i responses in the presence of nimodipine and ${\omega}$-conotoxin. Cyanidin-3-glucoside also significantly inhibited KCl (50 mM)-induced [$Ca^{2+}$]i increases. Cyanidin-3-glucoside significantly inhibited ATP-induced mitochondrial depolarization. The intracellular $Ca^{2+}$ chelator BAPTA-AM or the mitochondrial $Ca^{2+}$ uniporter inhibitor RU360 blocked the ATP-induced mitochondrial depolarization in the presence of cyanidin-3-glucoside. Cyanidin-3-glucoside blocked ATP-induced formation of ROS. BAPTA-AM further decreased the formation of ROS in the presence of cyanidin-3-glucoside. All these results suggest that cyanidin-3-glucoside inhibits ATP-induced calcium signaling in PC12 cells by inhibiting multiple pathways which are the influx of extracellular $Ca^{2+}$ through the nimodipine and ${\omega}$-conotoxin-sensitive and -insensitive pathways and the release of $Ca^{2+}$ from intracellular stores. In addition, cyanidin-3-glucoside inhibits ATP-induced formation of ROS by inhibiting $Ca^{2+}$-induced mitochondrial depolarization.

• 대한치과마취과학회지
• /
• 제14권2호
• /
• pp.101-106
• /
• 2014

Background: Remifentanil, an ultra-short-acting mu-opioid receptor agonist, is unique from other opioids because of its esterase-based metabolism, minimal accumulation, and very rapid onset and offset of clinical action. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. However, the effects of remifentanil on human keratinocyte and autophagy have yet to be fully elucidated during hypoxia-reoxygenation. Here we investigated whether remifentanil confers protective effect against hypoxia-reoxygenation in human keratinocyte and, if so, whether autophagy mediates this effect. Methods: The human keratinocytes were cultured under 1% oxygen tension. The cells were gassed with 94% $N_2$, and 5% $CO_2$ and incubated for 24 h at $37^{\circ}C$. To determine whether the administration of affects human keratinocytes hypoxia-reoxygenation injury, cells were then exposed to various concentrations of remifentanil (0.01, 0.1, 0.5 and 1 ng/ml) for 2 h. After remifentanil treatment, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at $37^{\circ}C$. Control group did not receive remifentanil treatment. Normoxia group did not receive hypoxia and remifentanil treatment for 36 h. 3-MA group was treated 3-methyladenine (3-MA) for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with MTT, showing the mitochondrial activity of living cells. Cells were stained with fluorescence and analyzed with Western blot analysis to find out any relations with activation of autophagy. Results: Prominent accumulation of autophagic specific staining MDC was observed around the nuclei in RPT group HaCaT cells. Similarly, AO staining, red fluorescent spots appeared in RPT group HaCaT cells, while the Normoxia, control and 3-MA groups showed mainly green cytoplasmic fluorescence. We here examined activation of autophagy related protein under H/R-induced cells by Western blotting analysis. Atg5, Beclin-1, LC3-II (microtubule-associated protein 1 light chain 3 form II) and p62 was elevated in RPT group cells. But they were decreased when autophagy was suppressed by 3-MA (Fig. 5). Conclusions: Although the findings of this study are limited to an in vitro interpretation, we suggest that remifentanil may have a beneficial effect in the recovery of wound from hypoxia-reoxygenation injury.