• International Journal of Oral Biology
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• 제44권2호
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• pp.50-54
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• 2019

Melatonin is a neurotransmitter that modulates various physiological phenomena including regulation and maintenance of the circadian rhythm. Nicotinic acetylcholine receptors (nAChRs) play an important role in oral functions including orofacial muscle contraction, salivary secretion, and tooth development. However, knowledge regarding physiological crosstalk between melatonin and nAChRs is limited. In the present study, the melatonin-mediated modulation of nAChR functions using bovine adrenal chromaffin cells, a representative model for the study of nAChRs, was investigated. Melatonin inhibited the nicotinic agonist dimethylphenylpiperazinium (DMPP) iodide-induced cytosolic free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) increase and norepinephrine secretion in a concentration-dependent manner. The inhibitory effect of melatonin on the DMPP-induced $[Ca^{2+}]_i$ increase was observed when the melatonin treatment was performed simultaneously with DMPP. The results indicate that melatonin inhibits nAChR functions in both peripheral and central nervous systems.

• 한국식품과학회지
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• 제51권2호
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• pp.160-168
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• 2019

AD는 뇌의 신경세포 사멸뿐만 아니라 학습 및 기억능 소실을 초래하는 퇴행성 뇌 질환이며, 기억과 관련된 주요 뇌 구역인 해마(hippocampus)는 콜린성 조절(cholinergic modulation)에 의해 영향을 받는다(Konishi 등, 2015). AD 병인에 대한 다양한 해석과 설명이 있으나 크게는 amyloid cascade hypothesis과 함께 cholinergic hypothesis가 주류를 이루고 있다. 몇몇의 연구에서 ChAT 합성, ACh 분비, nicotin 및 muscarinic 수용체 감소가 AD 뇌의 대뇌피질과 해마에서 관찰되어(Tata 등, 2014) 퇴행성 뇌질환에서의 중요성이 제시되었고, 이를 배경으로 한 acetylcholinesterase inhibitors (AChEI)가 AD 증상 완화의 목적으로 미국 FDA로부터 승인되어 시판되고 있다. 본 연구에서는 인삼의 활성 성분인 진세노사이드가 다량 함유된 PGBC가 $A{\beta}42$로 유도된 치매 모델에서 뇌세포 보호, ACh 분비 증가, 학습력/기억력 증가, ChAT 발현 증가를 확인하여 인삼열매 추출물의 치매 적용 여부를 확인하고자 하였다. 결과에서 언급한 바와 같이 PGBC는 익기 직전의 4년근 인삼 열매에 추출 및 발효 단계를 추가하여 확보된 물질로서, $A{\beta}42$ 섭취, 제거 및 ACh 분비 촉진 활성이 있는 Re, Rd, Rg3 함량이 증가되어(Kim 등, 2014; Jang 등, 2015), PGBC 자체로서 치매 인자에 대한 조절 효능이 예측되었다. 특히, 7증 7포 및 발효과정을 거친 이중가공 인삼 열매 추출물이 비 발효 증포 추출물에 비해 Rg3가 현저히 증가하는 사전 연구결과와 Rg3가 $A{\beta}42$ 제거 활성을 가지는 것으로 확인된 결과를 종합할 때 PGBC 투여가 AD 증상 완화의 조절자 역할을 할 것으로 생각된다(Kim 등, 2013; Jang 등 2015). 본 연구에 따르면, 마우스 치매 모델에 PGBC 처리 시 PAT 및 Morris water-maze test를 통해 대조군 대비 유의한 수준의 인지능력 개선, ACh 합성을 유도하는 ChAT 유전자 발현 증가, ACh 분비량 증가 등이 확인되어 전체적인 인지능 개선에 극적인 영향을 준 것으로 판단된다. 특히 $A{\beta}42$를 뇌 실로 주입(intracranial injection) 하여 나타나는 뇌세포 손상이 PGBC 투여를 통해 보호된 것으로 사료되었으며, 이는 주요 뇌세포 중 하나인 성상세포에서 관찰되는 GFAP 분석을 통해 확인되었다. 뇌 균질액을 이용한 AChE 활성 연구에서도 PGBC가 AChE를 현저하게 저해하는 것으로 확인되어, AD 환자에게 처방이 가능한 2대 의약품 군중 하나인 시냅스 내 신경전달물질 ACh bioavailability 증가 목적의 처방 보조요법 적용이 기대된다(${\check{C}}olovi{\acute{c}}$ 등, 2013). 결론적으로, 본 연구에 사용된 PGBC는 학습 및 기억력을 개선하는 활성물질을 포함하고 있어 1차적인 퇴행성 뇌질환 보조재로서 직간접적인 대증요법 역할과 2차적으로는 뇌 세포 보호를 통한 질병 악화 지연 소재로 개발이 기대되며, 보다 심도 있는 기전연구를 통해 천연물 신소재 개발도 가능할 것으로 사료된다.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.66-66
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• 1999

The negative chronotropic effect of ACh on heart fades in the continuous presence of ACh, which is known as a phenomenon called "vagal escape". The underlying mechanism of vagal escape is not entirely clear, but desensitization of acetylcholine-activated $K^{＋}$ currents ($K_{ACh}$) was suggested, at least in part, to be responsible.(omitted)d)

• BMB Reports
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• 제31권3호
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• pp.296-302
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• 1998

A potentiometric flow injection biosensor for the analysis of anti-cholinesterases (anti-ChEs), based on inhibition of enzyme activity, was developed. The sensor system consists of a reactor with acetylcholinesterase (AChE) immobilized on controlled pore glass and a detector with an $H^{+}-selective$ PVC-based membrane electrode. The principle of the analysis is based on the fact that the degree of inhibition of AChE by an anti-ChE is dependent on the concentration of the anti-ChE in contact with AChE. The sensor system was optimized by changing systematically the operating parameters of the sensor to evaluate the effect of the changes on sensor response to ACh. The optimized biosensor was applied to the analysis of paraoxon, an organophosphorus pesticide. Treatment of the inhibited enzyme with pyridine-2-aldoxime fully restored the enzyme activity allowing repeated use of the sensor.

• Journal of Korean Neurosurgical Society
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• 제56권6호
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• pp.500-503
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• 2014

If a ruptured blood blister-like aneurysm (BBA) arises from the lateral or superolateral wall of the internal carotid artery (ICA) at the level of the anterior choroidal artery (AChA), its proximity to the origin of the AChA presents a serious surgical challenge to preserve the patency of the AChA. Two such rare cases are presented, along with successful surgical techniques, including the application of a C-shaped aneurysm clip parallel to the ICA and a microsuture technique to repair the arterial defect. The patency of the AChA and ICA was successfully preserved without recurrence or rebleeding of the BBA during a 1-year follow-up after the operation.

• 한국환경보건학회지
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• 제29권3호
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• pp.43-49
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• 2003

ETS concentrations in the PC game rooms and factors affecting ETS concentrations were measured. Nicotine, 3-EP, respirable dust and UVPM were used as tracers for ETS. ETS concentrations are 2-3 times higher than those of other results. The concentration of ETS at the commercial district was higher than that of the residential district. The correlations between these tracers and SD/ ACH, a factor affecting to ETS concentration, were calculated. The correlation between 3-ethenylpyridine among tracers and SD/ACH was highest. The correlation between respirable dust and SD/ ACH was lowest. It was difficult to recommend respirable dust as a tracer of ETS.

• Molecular & Cellular Toxicology
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• 제2권3호
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• pp.216-221
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• 2006

The cholinesterase-inhibiting organophosphorous (OP) compounds known as nerve agents are highly toxic. The principal toxic mechanism of OP compounds is the inhibition of acethylcholine esterase (AChE) by phosphorylation of its catalytic site. The reversible competitive inhibition of AChE may prevent the subsequent OP intoxication. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed to investigate the relationship between the 29 compounds with structural diversity and their bioactivities against AChE. In particular, predictive models were constructed using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The results indicate reasonable model for CoMFA ($q^{2}=0.453,\;r^{2}=0.697$) and CoMSIA ($q^{2}=0.518,\;r^{2}=0.696$). The presence of steric and hydophobic group at naphtyl moiety of the model may lead to the design of improved competitive inhibitors for organophosphorous intoxication.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1999년도 춘계학술대회
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• pp.1-4
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• 1999

The potential therapeutic benefit of nicotinic ligands in a variety of neurodegenerative pathologies involving the CNS has energized research efforts to develop nicotinic acetylcholine receptor (nAChR) subtype-selective ligands. In particular, there has been a concerted effort to develop nicotinic compounds with selectivity for CNS nAChRs as potential pharmacological tools in the management of these disorders. The characterization of other novel nicotinic ligands such as epibatidine. showing a marked increase in potency at nAChRs, has provided additional support for the development of potent, selective ligands at individual nAChR subtypes. We have developed and studied a number of nicotinic compounds to identify potential candidates exhibiting such selectivity. In the present study, we report the synthesis and biological evaluations of some azabicyclic and azatricyclic nicotine analogs to decipher the relationship among steric requirements of the nicotine's pyrrolidine ring system, binding affinity and subtype-selectivity.

• Archives of Pharmacal Research
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• 제19권6호
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• pp.520-528
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• 1996

The involvement of the cyclic AMP (cAMP) effector system in the release of endogenous dopamine and acetylcholine from the rat neostriatum was assessed. Forskolin, an activator of adenylate cyclase, was used to enhance cAMP production, and the consequence of this enhancement on the spontaneous and potassium stimulated release of dopamine and acetylcholine was evaluated. Neostriatal slices were prepared from Fischer 344 rats and after a preincubation period the release of each endogenous neurotransmitter was measured from the same slice preparation. To measure acetylcholine release the slice acetylcholinesterase (AChE) activity was inhibited with physostigmine, but the release from slices with intact AChE activity was also determined (choline, instead of acetylcholine was detected in the medium). Under both conditions forskolin induced a significant dose-dependent increase in the potassium-evoked release of dopamine. In the same tissue preparations the release of neither acetylcholine (AChE inhibited) nor choline (AChE intact) was affected by forskolin. The results indicate that the CAMP second messenger system might be involved in neuronal mechanisms that enhance neostriatal dopamine release, but stimulation of this second messenger by forskolin does not further enhance neostriatal acetylcholine release.

• Biomolecules & Therapeutics
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• 제9권2호
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• pp.119-124
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• 2001

In order to determine the role of dehydroepiandrosterone (DHEA), the important sex-steroid hormone precursor, in vascular reactivity in rats, animals were treated for two weeks with DHEA or sex hormones, and the vascorelaxant and contractile responses of isolated aorta were examined. DHEA diminished the acetylcholine (ACh)-induced relaxation in female rats, while the drug was without effect in males. Testoterone lowered the vasorelaxant activity to ACh in either sex. 17$\beta$-Estradiol enhanced ACh-induced vasorelaxation in male rats, but this female sex hormone did not influence in females. In male rats, the androgen receptor antagonist flutamide also enhanced vasorelaxant action of ACh. When the male rat aorta was incubated in vitro with a nitric oxide (NO) synthase inhibitor L-NAME, phenylephrine-induced contraction was greatly potentiated in DHEA-pretreated rats compared to control ones. The present results suggest that DHEA stimulates mainly androgen in female, but both androgen and estrogen in male rats. The participation of NO In the modulation of vascular reactivity with pretreated DHEA was also considered.