• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.81-96
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• 2005

This experiment was designed to investigate the effect of Dichroa febrifuga(DIF) on the Alzheimer’s disease. The effects of DIF extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by $A{\beta}$ plus LPS and amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. DIF extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. DIF extract suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. DIF extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. DIF extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. DIF extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that DIF extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.713-719
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• 2018

Dipeptidyl peptidase4 (DPP4) inhibitors such as gemigliptin are antidiabetic drugs elevating plasma concentration of incretins such as GLP-1. In addition to the DPP4 inhibition, gemigliptin might directly improve the functions of vessels under pathological conditions. To test this hypothesis, we investigated whether the acetylcholine-induced endothelium dependent relaxation (ACh-EDR) of mesenteric arteries (MA) are altered by gemigliptin pretreatment in Spontaneous Hypertensive Rats (SHR) and in Wistar-Kyoto rats (WKY) under hyperglycemia-like conditions (HG; 2 hr incubation with 50 mM glucose). ACh-EDR of WKY was reduced by the HG condition, which was significantly recovered by $1{\mu}M$ gemigliptin while not by saxagliptin and sitagliptin up to $10{\mu}M$. The ACh-EDR of SHR MA was also improved by $1{\mu}M$ gemigliptin while similar recovery was observed with higher concentration ($10{\mu}M$) of saxagliptin and sitagliptin. The facilitation of ACh-EDR by gemigliptin in SHR was not observed under pretreatment with NOS inhibitor, L-NAME. In the endothelium-denuded MA of SHR, sodium nitroprusside induced dose-dependent relaxation was not affected by gemigliptin. The ACh-EDR in WKY was decreased by treatment with $30{\mu}M$ pyrogallol, a superoxide generator, which was not prevented by gemigliptin. Exendin-4, a GLP-1 analogue, could not enhance the ACh-EDR in SHR MA. The present results of ex vivo study suggest that gemigliptin enhances the NOS-mediated EDR of the HG-treated MA as well as the MA from SHR via GLP-1 receptor independent mechanism.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.55-61
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• 1999

The present experiments were performed to examine the effects of acetylcholine (ACh) and carbachol (CC) on thyroxine ($T_4$) release and any possible relation between inhibition of $T_4$ release and signaling pathway in guinea pig thyroids. The thyroids were incubated in the medium containing the test agents, samples of the medium were assayed for $T_4$ by EIA kits. ACh and CC inhibited the TSH-stimulated $T_4$ release. These inhibition were reversed by atropine, but not by d-tubocurarine. The inhibitory effects of ACh on $T_4$ release were prevented by $M_{1^-}$ and $M_{3^-}$muscarinic antagonists and its inhibition was also slightly reversed by $M_{2^-}$ and $M_{4^-}$muscarinic antagonists. R59022, like ACh and CC, also inhibited the TSH-stimulated $T_4$ release. This inhibition was reversed by protein kinase C inhibitor and $Ca^{2+}$ channel blocker. The present study suggests that cholinergic inhibition of $T_4$ release from thyroids can be induced mainly by activation of the $M_{1^-}$ or $M_{3^-}$ receptors and that it is mediated through the muscarinic receptorstimulated protein kinase C activation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.130-138
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• 2005

This experiment was designed to investigate the effect of Phellodendron amurense(PLDA) on the Alzheimer's disease. The effects of PLDA extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. PLDA extract suppressed $IL-1{\beta}$, IL-6, APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ ; AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$. PLDA extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. PLDA extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that PLDA extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.2
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• pp.91-99
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• 2012

Airborne chlorpyrifos concentrations in formulation workplaces have not been determined in Korea. The aim of the study was to evaluate chlorpyrifos concentrations of air in a formulation workplace and recognize the RBC cholinesterase activities for the formulation workers. 30 air samples (personal or area sampling) were collected and bood samples from 10 workers were collected for RBC chlorinesterase (RBC AChE) activity in a factory on May 2008. Air samples were collected by the National Institute for Occupational Safety and Health (NIOSH) method and were analyzed by GC-MS. Airborne chlorpyrifos concentrations ranged from 0.003 to $12.90mg/m^3$ and geometric mean (GM) was $0.15\;mg/m^3.$ Compared to Korean Occupational Exposure Limit (KOEL) of 0.1 (2011) or $0.2\;mg/m^3$ (2008), at 95% confidence, airborne concentrations exceeded the KOEL 69.7% or 56.1% of the time or less, indicating that this concentration level was unacceptable according to exposure assessment using a LogNorm2$^{(R)}$. Since the workers were continually at work on the organophosphate or carbamate pesticides formulation, individual baseline for RBC AChE activity was not determined. As the results of comparison with reference average value of RBC AChE activity, it was found that a worker was below 70% RBC AChE activity and five workers were abnormal.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.5
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• pp.273-282
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• 2006

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10\;{\mu}M)$, an activator of L-type $Ca^2+$ channels and cyclopiazonic acid $(10\;{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were also inhibited. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• The Journal of the Convergence on Culture Technology
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• v.8 no.3
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• pp.291-296
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• 2022

This study was conducted on curcumin which had increased bioavailability as a potential AChE inhibitor for the treatment of neurodegenerative diseases. The purpose of this study is to confirm the in vitro neuroprotective effect on Aricumin (turmeric extract). To confirm the neuroprotective effect, AChE inhibition for Aricumin was evaluated, and cell viability was analyzed for HT-22cell, and oxidative stress (glutamate, H₂O₂)-induced HT-22 cytotoxicity was evaluated. As a result of the change in the AChE inhibition rate of Aricumin (Turmeric extract), it was confirmed that Aricumin at a concentration of 39.06㎍/ml or higher inhibited AChE activity by about 20% and more. And it was confirmed that the cytotoxicity of HT-22 cells induced by oxidative stress (Gluamate 5 mM and H₂O₂ 500 µM) was significantly inhibited from 0.01 to 0.1 mg/ml concentration (p<005). These results suggest that Aricumin (turmeric extract) have potential neuroprotective effects.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.37-43
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• 2005

Our previous report demonstrated that chick myoblasts are equipped with $Ca^{2+}$-permeable stretchactivated channels and $Ca^{2+}-activated$ potassium channels ($K_{Ca}$), and that hyperpolarization-induced by $K_{Ca}$ channels provides driving force for $Ca^{2+}$ influx through the stretch-activated channels into the cells. Here, we showed that acetylcholine (ACh) also hyperpolarized the membrane of cultured chick myoblasts, suggesting that nicotinic acetylcholine receptor (nAChR) may be another pathway for $Ca^{2+}$ influx. Under cell-attatched patch configuration, ACh increased the open probability of $K_{Ca}$ channels from 0.007 to 0.055 only when extracellular $Ca^{2+}$ was present. Nicotine, a nAChR agonist, increased the open probability of $K_{Ca}$ channels from 0.008 to 0.023, whereas muscarine failed to do so. Since the activity of $K_{Ca}$ channel is sensitive to intracellular $Ca^{2+}$ level, nAChR seems to be capable of inducing $Ca^{2+}$ influx. Using the $Ca^{2+}$ imaging analysis, we were able to provide direct evidence that ACh induced $Ca^{2+}$ influx from extracellular solution, which was dramatically increased by valinomycin-mediated hyperpolarization. In addition, ACh hyperpolarized the membrane potential from $-12.5{\pm}3$ to $-31.2{\pm}5$ mV by generating the outward current through $K_{Ca}$ channels. These results suggest that activation of nAChR increases $Ca^{2+}$ influx, which activates $K_{Ca}$ channels, thereby hyperpolarizing the membrane potential in chick myoblasts.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.51-51
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• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.29-35
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• 2005

To prove the buffering contribution of mitochondria to the increase of intracellular $Ca^{2+}$ level ($[Ca^{2+}]_i$) via background nonselective cation channel (background NSCC), we examined whether inhibition of mitochondria by protonophore carbonylcyanide m-chlorophenylhydrazone (CCCP) affects endothelial $Ca^{2+}$ entry and $Ca^{2+}$ buffering in freshly isolated rabbit aortic endothelial cells (RAECs). The ratio of fluorescence by fura-2 AM ($R_{340/380}$) was measured in RAECs. Biological state was checked by application of acetylcholine (ACh) and ACh ($10{\mu}M$) increased $R_{340/380}$ by $1.1{\pm}0.15$ ($mean{\pm}S.E.$, n=6). When the external $Na^+$ was totally replaced by $NMDG^+$, $R_{340/380}$ was increased by $1.19{\pm}0.17$ in a reversible manner (n=27). $NMDG^+$-induced $[Ca^{2+}]_i$ increase was followed by oscillatory decay after $[Ca^{2+}]_i$ reached the peak level. The increase of $[Ca^{2+}]_i$ by $NMDG^+$ was completely suppressed by replacement with $Cs^+$. When $1{\mu}M$ CCCP was applied to bath solution, the ratio of $[Ca^{2+}]_i$ was increased by $0.4{\pm}0.06$ (n=31). When $1{\mu}M$ CCCP was used for pretreatment before application of $NMDG^+$, oscillatory decay of $[Ca^{2+}]_i$ by $NMDG^+$ was significantly inhibited compared to the control (p＜0.05). In addition, $NMDG^+-induced$ increase of $[Ca^{2+}]_i$ was highly enhanced by pretreatment with $2{\mu}M$ CCCP by $320{\pm}93.7$%, compared to the control ($mean{\pm}S.E.$, n=12). From these results, it is concluded that mitochondria might have buffering contribution to the $[Ca^{2+}]_i$ increase through regulation of the background NSCC in RAECs.