• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.339-350
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• 1999

The present study was attempted to examine the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. The perfusion of PACAP (10 nM) into an adrenal vein for 60 min produced a great inhibition in CA secretion evoked by ACh $(5.32{\times}10^{-3}\;M),$ high $K^+\;(5.6{\times}10^{-2}\;M),$ DMPP $(10^{-4}\;M\;for\;2\;min),$ McN-A-343 $(10^{-4}\;M\;for\;2\;min),$ cyclopiazonic acid $(10^{-5}\;M\;for\;4\;min)$ and Bay-K-8644 $(10^{-5}\;M\;for\;4\;min).$ Also, in the presence of neuropeptide (NPY), which is known to be co-localized with norepinephrine in peripheral sympathetic nerves, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with PACAP (10 nM) under the presence of VIP antagonist $[(Lys^1,\;Pro^{2.5},\;Arg^{3.4},\;Tyr^6)-VIP\;(3\;{\mu}M)]$ for 20 min, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not altered greatly in comparison to the case of PACAP-treatment only. Taken together, these results suggest that PACAP causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells.

• Archives of Pharmacal Research
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• 제24권3호
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• pp.240-248
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• 2001

The present study was attempted to investigate the effect of quinine on secretion of catecholamines (CA) etroked by cholinergic stimulation and membrane depolarization from the isolated perfused rat adrenal gland. The perfusion of quinine (15-150${\mu}$M) into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretion evoked by ACh ($5.32{\times}10^{-3}M$), high $K^{+}5.6{\times}10^{-2}M$, DMPP ($10^{-4}M$ for 2 min), McN-A-343 ($10^{-4}M$ for 2 min), cyclopiazonic acid ($10^{-5}$ for 4 min) and Bay-K-8644 ($10^{-5}$ M for 4 min). Also, under the presence of pinacidil ($10^{-4}$ M), which is also known to be a selective potassium channel activator, CA secretory responses evoked by ACh, high potassium, DMPP McN-A-343, Bay-K-8644 and cyclopiazonic acid were also greatly reduced. When preloaded along with quinine ($5{\times}10^{-5}M$) and glibenclamide ($10^{-6}$ M), a specific blocker of ATP-regulated potassium channels, CA secretory responses evoked by ACh, high potassium, DMPP McN-A-343, Bay-K-8644 and cyclopiazonic acid were recovered as compared to those of quinine-treatment only. taken together, these results demonstrate that quinine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization through inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenmodullary chromaffin cells. These findings suggest that activation of potassium channels may be involved at least in inhibitory action of quinine on CA secretion from the rat adrenal gland.

• The Korean Journal of Physiology and Pharmacology
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• 제11권1호
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• pp.21-30
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• 2007

The present study was designed to establish comparatively the inhibitory effects of cilnidipine(CNP), nifedipine(NIF), and $\omega$-conotoxin GVIA(CTX) on the release of CA evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. CNP(3 ${\mu}M$), NIF(3 ${\mu}M$), and CTX(3 ${\mu}M$) perfused into an adrenal vein for 60 min produced greatly inhibition in CA secretory responses evoked by ACh($5.32{\times}10^{-3}M$), DMPP($10^{-4}M$ for 2 min), McN-A-343($10^{-4}M$ for 2 min), high $K^+(5.6{\times}10^{-2}M)$, Bay-K-8644($10^{-5}M$), and cyclopiazonic acid($10^{-5}M$), respectively. For the CA release evoked by ACh and Bay-K-8644, the following rank order of potency was obtained: CNP>NIF>CTX. The rank order for the CA release evoked by McN-A-343 and cyclopiazonic acid was CNP>NIF>CTX. Also, the rank orders for high $K^+$ and for DMPP were NIF>CTX>CNP and NIF>CNP>CTX, respectively. Taken together, these results demonstrate that all voltage-dependent $Ca^{2+}$ channels(VDCCs) blockers of cilnidipine, nifedipine, and $\omega$-conotoxin GVIA inhibit greatly the CA release evoked by stimulation of cholinergic(both nicotinic and muscarinic) receptors and the membrane depolarization without affecting the basal release from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effects of cilnidipine, nifedipine, and $\omega$-conotoxin GVIA are mediated by the blockade of both L- and N-type, L-type only, and N-type only VDCCs located on the rat adrenomedullary chromaffin cells, respectively, which are relevant to $Ca^{2+}$ mobilization. It is also suggested that N-type VDCCs play an important role in the rat adrenomedullary CA secretion, in addition to L-type VDCCs.

• Animal cells and systems
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• 제16권3호
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• pp.198-206
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• 2012

Anxiety in zebrafish can be determined by examining their bottom-dwelling and light-avoidance behavior. This study determines the effects of physostigmine and scopolamine on anxiety in zebrafish by measuring swimming frequency for three horizontal layers and three vertical columns of a water test tank illuminated by a light source located above the central surface of the tank. In the 1 h session, zebrafish in the control group preferred the bottom layer the most and the center column the least. Zebrafish treated with 2-20 ${\mu}M$ physostigmine were more likely to prefer the to layer than controls, and there were significant pairwise differences between physostigmine-treated zebrafish and controls, indicating the anxiolytic effect of physostigmine. Further, 10 and $20{\mu}M$ physostigmine-treated zebrafish no longer avoided the center column. Scopolamine had no anxiolytic effect on bottom-dwelling and light-avoidance behaviors but suppressed the anxiolytic effect of physostigmine. In terms of their preference for various zones formed by layers and columns, zebrafish in the control group preferred the bottom left and right zones the most. Physostigmine had a positive effect on the preference for the top center zone, which was suppressed by scopolamine pretreatment. The results suggest that the level of anxiety in zebrafish can be reduced by activating acetylcholinergic neurotransmitter systems, which is mediated in part by muscarinic receptors.

• Fisheries and Aquatic Sciences
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• 제25권2호
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• pp.49-63
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• 2022

Anti-cholinesterase (ChE)s are commonly prescribed as the symptomatic treatment of Alzheimer's disease. They are applied to prevent the breakdown of neurotransmitter acetylcholine (ACh) that bind to muscarinic and nicotinic receptors in the synaptic cleft. Seaweeds are one of the richest sources of bioactive compounds for both nutraceuticals and pharmacognosy applications. This study aimed to determine the anti-ChEs activity of Gracilaria manilaensis, one of the red seaweeds notables for its economic importance as food and raw materials for agar production. Methanol extracts (GMM) of G. manilaensis were prepared through maceration, and further purified with column chromatography into a semi-pure fraction. Ellman assay was carried out to determine the anti-acetylcholinesterase (AChE) and anti-butyrylcholinesterase (BuChE) activities of extracts and fractions. Lineweaver-Burk plot analysis was carried out to determine the inhibition kinetic of potent extract and fraction. Major compound(s) from the most potent fraction was determined by liquid chromatography-mass spectrometry (LCMS). GMM and fraction G (GMMG) showed significant inhibitory activity AChE with EC₅₀ of 2.6 mg/mL and 2.3 mg/mL respectively. GMM and GMMG exhibit mixed-inhibition and uncompetitive inhibition respectively against AChE. GMMG possesses neuroprotective compounds such as cynerine A, graveolinine, militarinone A, eplerenone and curumenol. These findings showed a promising insight of G. manilaensis to be served as a nutraceutical for neuronal health care in the future.

• Nutrition Research and Practice
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• 제17권2호
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• pp.192-205
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• 2023

BACKGROUND/OBJECTIVES: It is known that the renin-angiotensin system (RAS) in the brain could regulate cognitive functions as well as blood pressure. Inhibition of RAS for the improvement of cognitive function may be a new strategy, but studies so far have mostly reported on the effects of RAS inhibition by drugs, and there is no research on cognitive improvement through RAS inhibition of food ingredients. Therefore, this study investigated the effect of curcumin on blood pressure and cognitive function and its related mechanism in spontaneously hypertensive rat/Izm (SHR/Izm). MATERIALS/METHODS: Six-week-old SHR/Izm rats were divided into 5 groups: control group (CON), scopolamine group (SCO, drug for inducing cognitive deficits), positive control (SCO and tacrine [TAC]), curcumin 100 group (CUR100, SCO + Cur 100 mg/kg), and curcumin 200 group (CUR200, SCO + Cur 200 mg/kg). Changes in blood pressure, RAS, cholinergic system, and cognitive function were compared before and after cognitive impairment. RESULTS: The SCO group showed increased blood pressure and significantly reduced cognitive function based on the y-maze and passive avoidance test. Curcumin treatments significantly improved blood pressure and cognitive function compared with the SCO group. In both the CUR100 and CUR200 groups, the mRNA expressions of angiotensin-converting enzyme (ACE) and angiotensin II receptor type1 (AT1), as well as the concentrations of angiotensin II (Ang II) in brain tissue were significantly decreased. The mRNA expression of the muscarinic acetylcholine receptors (mAChRs) and acetylcholine (ACh) content was significantly increased, compared with the SCO group. CONCLUSIONS: The administration of curcumin improved blood pressure and cognitive function in SCO-induced hypertensive mice, indicating that the cholinergic system was improved by suppressing RAS and AT1 receptor expression and increasing the mAChR expression.

• 대한약리학회지
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• 제25권1호
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• pp.31-42
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• 1989

Metoclopramide (MCP)는 역류성식도염, 위하수증, 항암제에 의한 구토 증상을 치료하는데 사용되고 있는 dopamine수용체 차단제로 알려져 있다. 본 연구에서는 흰쥐의 적출 관류부신에서 catecholamine (CA)의 분비작용에 미치는 영향을 검토하여 다음과 같은 결과를 얻었다. MCP는 부신정맥내로 주입하였을때 용량의존적으로 CA 분비작용을 나타냈다. 이러한 MCP의 CA 분비작용은 atropine 전처치로 차단되었으나 chlorisondamine 처치에 의해서는 완전 차단되지 못하였다. MCP 분비작용은 physostigmine, adenosine, ouabain의 전처치로 현저히 증강되었다. 그러나 5mM-EGTA 함유 $Ca^{++}-free\;Krebs$ 액으로 관류하였을때 MCP의 CA 분비작용은 현저히 억제되었다. MCP (200 ug/30 min)를 관류한 실험에서는 KCI이나 acetylcholine의 CA 분비작용이 유의있게 감소되었다. 이상의 실험결과로 보아 MCP는 칼슘의존적기전에 의해 CA를 유리 시키며, 이러한 분비작용은 부신에서 nicotine수용체 보다도 muscarine수용체의 활성화에 더 기인 되는 것으로 생각되며, chromaffin cell에 대한 일분 직접작용도 개재되어 나타나는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.155-164
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• 2008

Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10${\sim}100{\mu}$M) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_n$ receptor agonist, 100${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100${\mu}$M) in both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30${\mu}$M), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent$Na^+$ channels, 100${\mu}$M), Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10${\mu}$M), and cyc1opiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10${\mu}$M) were significantly reduced. In the simultaneous presence of resveratrol (30${\mu}$M) and L-NAME (an inhibitor of NO synthase, 30${\mu}$M), the CA secretory evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyc1opiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through $Na^+$ and $Ca^{2+}$ channels into the adrenomedullary cells as well as by blocking the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.

• Journal of Yeungnam Medical Science
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• 제8권2호
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• pp.138-149
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• 1991

흰쥐(Sprague-Dawley)의 방광에서 적출한 배뇨근절편을 적출 근편 실험조에 현수하고, 등척성 장력 측정기를 사용하여 그 수축력을 묘기하였다. 배뇨근 절편은 전기장자극에 의해 수축하였으며, 이 수축반응은 콜린에스테라제 억제약물인 physostigmine에 의해 증가하였고 신경말단에서의 choline 재흡수를 방해하는 hemicholinium에 의해 억제되었으며, 신경절봉쇄약물인 hexamethonium에 의해서는 영향을 받지 않았으나 신경축색전도 억제제인 tetrodotoxin에 의해서 소실되었다. 이러한 전기장자극유발 수축은 콜린성 무스카린성 수용체봉쇄약물인 atropine에 의해 부분적으로 길항되었으며, atropine에 의해 길항되지 않는 부분은 ATP 탈감작에 의해 완전히 소실되었다. 배뇨근 절편은 콜린성 무스카린성 수용체 흥분제인 bethanechol과 퓨린성 수용체 흥분제인 ATP에 의하여 농도의존적 수축력 증가를 나타내었으며, 이중 bethanechol 유발수축은 ATP 탈감작에 의해 영향을 받지 않았고, ATP 유발수축은 tetrodotoxin에 의하여 영향을 받지 않았다. 이상의 결과로 보아 흰쥐의 적출배뇨근에는 흥분성 신경전달체계로서 퓨린성 수용체와 콜린성 수용체가 존재하며, 이들은 서로 영향을 미침이 없이 독자적으로 배뇨근 수축에 기여하고 있다고 사료된다.

• 대한약리학회지
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• 제27권1호
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• pp.53-67
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• 1991

흰쥐 적출 부신에서 DMPP와 McN-A-343의 카테콜아민(CA) 분비작용의 차이와 특성에 대해서 연구한 결과 다음과 같다. DMPP(100 uM)와 McN-A-343(100 uM)은 부신정맥내로 투여시 유의한 카테콜아민 분비작용을 나타내었다. Mol농도로 비교시 McN-A-343의 CA분비작용은 DMPP의 약 1/5정도였다. DMPP나 McN-A-343의 반복투여시 반응 급강현상은 관찰할 수 없었다. DMPP의 CA분비작용은 chlorisondamine이나 desipramine또는 $Ca^{2+}-free$ Krebs + EGTA 관류등의 전처치로 의의있게 억제되었으나, pirenzepine, ouabain 및 physostigmine등 전처치에 의해서는 영향을 받지 않았다. 그러나 atropine 전처치시 DMPP의 분비작용은 오히려 증강되었다. McN-A-343의 CA분비작용은 atropine, pirenzepine, chloriondamine, physostigmine 및 $Ca^{2+}-free$ medium plus EGTA 관류등의 전처치에 의해서현처히 차단되었으나 desipramine등에 의해서는 영향을 받지 않았다. 그러나 ouabain의 전치치시 McN-A-343의 분비효과는 크게 증강되었다. 이상의 실험결과로 보아 DMPP와 McN-A-343은 횐쥐 적출관류 부신에서 현저한 CA분비작용을 일으키며, 이는 $Ca^{2+}$ 의존성 임을 보였으며, DMPP의 분비작용은 부신의 nicotine 수용체의 흥분을 통해서 나타내며, 또한 McN-A-343의 분비작용은 $M_{1}-muscarine$ 수용체의 흥분에 의하여 유발되는 것을 생각된다. DMPP의 분비활성이 McN-A-343보다 훨씬 강력한 것으로 사료된다.