• Title/Summary/Keyword: nAChR

Search Result 37, Processing Time 0.022 seconds

Quantitative Structure Activity Relationship between Diazabicyclo-[4.2.0]octanes Derivatives and Nicotinic Acetylcholine Receptor Agonists

  • Kim, Eun-Ae;Jung, Kyoung-Chul;Sohn, Uy-Dong;Im, Chae-Uk
    • The Korean Journal of Physiology and Pharmacology
    • /
    • v.13 no.1
    • /
    • pp.55-59
    • /
    • 2009
  • Three dimensional quantitative structure activity relationship between diazabicyclo[4.2.0]octanes and nicotinic acetylcholine receptor($h{\alpha}4{\beta}2$ and $h{\alpha}3{\beta}4$) agonists was studied using comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA). From 11 CoMFA and CoMSIA models, CoMSIA with steric and electrostatic fields gave the best predictive models($q^2=0.926$ and 0.945, ${r^2}_{ncv}=0.983$ and 0.988). This study can be used to develop potent $h{\alpha}4{\beta}2$ receptor agonists with low activity on $h{\alpha}3{\beta}4$ subtype.

The Effects of Cimicifuga Racemosa Extracts on the Inhibition of Catecholamine Secretion in Bovine Chromaffin Cells (부신수질 크로마핀(Chromaffin) 세포를 이용한 승마 추출무의 카테콜라민 분비 저해작용)

  • Woo, Kyung-Chul;Suh, Byung-Sun
    • Korean Journal of Pharmacognosy
    • /
    • v.34 no.4 s.135
    • /
    • pp.318-323
    • /
    • 2003
  • Extracts of Black cohosh (Cimicifugae rhizoma) have been used for the treatment of climacteric complaints for decades. A significant number of woman entering menopause exhibit the following symptoms: getting hot flushes, night sweats, irritability, depression, and anxiety, A reduction of the frequency of hot flushes equivalents and hints on the antidepressant activity of Cimcifuga extracts. In the present work, we have screened several 80% ethanol extracts from medicinal plants and found that the extracts from Cimicifugae Rhizoma(Black cohosh:승마) have inhibitory effect on catecholamine secretion in bovine chromaffin cell. Since this extract inhibited 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP)-induced catecholamine secretion, but did not inhibit KCl, bradykinin, and veratridine-evoked case, this inhibitory effect is mediated by nicotinic acetylcholine receptors with noncompetitive manner.

Anesthetic considerations for a patient with myasthenia gravis undergoing deep sedation in an outpatient oral surgery setting

  • Prabhu, Shamit S.;Khan, Saad A.;Doudnikoff, Alexander L.;Reebye, Uday N.
    • Journal of Dental Anesthesia and Pain Medicine
    • /
    • v.19 no.1
    • /
    • pp.67-72
    • /
    • 2019
  • Myasthenia gravis (MG) is a neuromuscular autoimmune disorder which clinically presents as muscular weakness and fatigue due to autoantibody formation against acetylcholine receptors (AChR), leading to their subsequent destruction. Due to the neuromuscular implications of MG, certain considerations must be taken into account when providing anesthesia to MG patients. In the following case report, we have outlined procedural considerations for the anesthetic management of a patient with MG undergoing deep sedation for an elective oral surgery in an outpatient setting, as well as a discussion of relevant literature.

Cellular Mechanism of Nicotine-mediated Intracellular Calcium Homeostasis in Primary Culture of Mouse Cerebellar Granule Cells (니코틴의 마우스 소뇌과립세포내 칼슘의 항상성 조절기전)

  • Kim, Won-Ki;Pae, Young-Sook
    • The Korean Journal of Pharmacology
    • /
    • v.32 no.1
    • /
    • pp.13-21
    • /
    • 1996
  • Intracellular calcium concentration ($[Ca^{2+}]_i$) may play a crucial role in a variety of neuronal functions. Here we report that in primary culture of mouse cerebellar granule cells nicotinic acetylcholine receptors (nAChRs) are expressed in a specific developmental stage and involved in the regulation of intracellular calcium homeostasis. Nicotine-mediated calcium responses were measured using $^{45}Ca^{2+}$ or fluorometrically using the calcium-sensitive fluorescent dye fura-2. Maximal uptake of $^{45}Ca^{2+}$ evoked by nicotine in mouse cerebellar granule cells were revealed $8{\sim}12$ days in culture. In contrast, nicotine did not alter the basal $^{45}Ca^{2+}$ uptake in cultured glial cells. In cerebellar granule cells nicotine-evoked $^{45}Ca^{2+}$ uptake was largely blocked by the NMDA receptor antagonists. Glutamate pyruvate transaminase (GPT). which removes endogenous glutamate, also prevented nicotine effects, implying the indirect involvement of glutamate in nicotine-mediated calcium responses. Fluorometric studies using fura-2 showed two phases of nicotine-evoked $[Ca^{2+}]_i$ rises: the initial rising phase and the later plateau phase. Interestingly, the NMDA receptor antagonists and GPT appeared to inhibit only the later plateau phase of nicotine-evoked $[Ca^{2+}]_i$ rises. The present results imply that nicotine mediated $^{45}Ca^{2+}$ uptake and $[Ca^{2+}]_i$ rises are attributed to the calcium fluxes through both nAchRs and NMDA receptors in a time-dependent manner. Consequently, nAChRs may play an important role in neuronal development by being expressed in a specific developmental stage and regulating the intracellular calcium homeostasis.

  • PDF

Gene Expression Profile of the Responder vs. the Non-Responder to the Acupuncture Mediated Analgesic Effects (침자극에 대한 반응과 비반응군 흰쥐의 특이 유전자 발현 연구)

  • Sur Young Chan;Rho Sam Woong;Lee Gi Seog;Ko Eun Jung;Hong Moo Chang;Shin Min Kyu;Min Byung il;Bae Hyun Su
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.17 no.3
    • /
    • pp.633-642
    • /
    • 2003
  • A pain is the symptom which defends against noxious stimulus about a human body, it is known that if the periphery of perceptive nerve were stimulated by a physical or chemical factors, the stimulation is induced by transmission to pain center in the cerebral cortex according to pain conduction tract. The treatment of pain is to decrease a stimulus that causes a pain or block off a nerve transmitting a stimulus or puts on a way to calm down pain center, but It is for adjustment of a pain to be the most representative in acupuncture among various ways to cure a pain in Oriental medicine. However, the analgesic effect of an individual response to acupuncture stimulation shows marked individual variations, so these days genetic a few approach is attempted. On this the author determined that the responding group was appointed those whose tail flick latency (TFL) responding time delayed the minimum of 30 % comparing with basal reaction time. For those whose TFL time had shorter than 30 % was grouped as a non-responding group. And then the hypothalamus of each group was dissected and RNA was further purified. After synthesizing cDNA using oligo dT primer, products were finally applied to the PCR. The results were as follows; The ratio of responding group to non-responding group was 6:4. Ach T (acetylcholinesterase T subunit), BF-I (Brain factor-I), DBH (Dopamine β-hydroxylase) and PNM (Phosphotidylethanolamine N-Methyltransferase) were revealed significantly in the responding group. Cathepsin B and Tau were revealed significantly in the non-responding group. The PCR results show that Ach T, BF-I, DBH and PNM are expressed abundantly in the responding group, where as cathepsin B and tau are abundant in the non-responding group. These results suggest that the analgesic effect on acupuncture stimulation is related to regulation of neurotransmitter as well as neurodegeration of cerebrum.

Assessment of hazardous substances and workenvironment for cleanrooms of microelectronic industry (전자산업 청정실의 작업환경 및 유해물질농도 평가)

  • Chung, Eun-Kyo;Park, Hyun-Hee;Shin, Jung-Ah;Jang, Jae-Kil
    • Journal of Korean Society of Occupational and Environmental Hygiene
    • /
    • v.19 no.3
    • /
    • pp.280-287
    • /
    • 2009
  • High-tech microelectronics industry is known as one of the most chemical-intensive industries. In Korea, Microelectronics industry occupied 38% of export and 16% of working employees work in microelectronics industry. But, chemical information and health hazards of high-tech microelectronics manufacturing are poorly understood because of rapid development and its penchant for secrecy. We need to investigate on chemical use and exposure control. We Site-visits to 6 high-tech microelectronics manufacturing company which have cleanroom work using over 1,000kg organic solvents (5 semi-conductor chips and its related parts company, 1 liquid crystal display (LCD)). We reviewed their data on chemical use and ventilation system, and measured TVOCs (Total Volatile Organic Compounds) and carbon dioxide concentration. All cleanroom air passed through hepa filters to acheive low particle levels and only 1 cleanroom uses carbon filters to minimize the organic solvents exposures In TVOC screening test, Cleanroom for semi-conductor chips and its related parts company with laminar down flow system (e.g. class 1~100) showed nondetectable level of TVOCs concentration, but Cleanroom for liquid crystal display (LCD) with conventional flow system (e.g. class 1,000~10,000) showed 327 ppm as TVOCs. Acetone concentration in cleanroom for Jig cleaning, LC Injection, Sealing processes were 18.488ppm (n=14), 49.762 ppm (n=15), 8.656 ppm (n=14) as arithmetric mean. Acetone concentration in cleanroom for LCD inspection process was 40ppm (n=55) as geometric mean, where the range was 7.8~128.7ppm and weakly correlated with ventilation rate efficiency(r=0.44, p<0.05). To control organic solvents in cleanrooms, chemical and carbon filters should be installed with hepa filters. Even though their volatile organic compounds concentration was not exceed to occupational exposure limits, considering of entrance limited cleanroom environment, long-term period exposure effects and adverse health effects of cleanroom worker need further reseach.

Anti-stress effects of ginseng via down-regulation of tyrosine hydroxylase (TH) and dopamine ${\beta}$-hydroxylase (DBH) gene expression in immobilization-stressed rats and PC12 cells

  • Kim, Yang-Ha;Choi, Eun-Ha;Doo, Mi-Ae;Kim, Joo-Yeon;Kim, Chul-Jin;Kim, Chong-Tai;Kim, In-Hwan
    • Nutrition Research and Practice
    • /
    • v.4 no.4
    • /
    • pp.270-275
    • /
    • 2010
  • Catecholamines are among the first molecules that displayed a kind of response to prolonged or repeated stress. It is well established that long-term stress leads to the induction of catecholamine biosynthetic enzymes such as tyrosine hydroxylase (TH) and dopamine ${\beta}$-hydroxylase (DBH) in adrenal medulla. The aim of the present study was to evaluate the effects of ginseng on TH and DBH mRNA expression. Repeated (2 h daily, 14 days) immobilization stress resulted in a significant increase of TH and DBH mRNA levels in rat adrenal medulla. However, ginseng treatment reversed the stress-induced increase of TH and DBH mRNA expression in the immobilization-stressed rats. Nicotine as a ligand of the nicotinic acetylcholine receptor (nAChR) in adrenal medulla stimulates catecholamine secretion and activates TH and DBH gene expression. Nicotine treatment increased mRNA levels of TH and DBH by 3.3- and 3.1-fold in PC12 cells. The ginseng total saponin exhibited a significant reversal in the nicotine-induced increase of TH and DBH mRNA expression, decreasing the mRNA levels of TH and DBH by 57.2% and 48.9%, respectively in PC12 cells. In conclusion, immobilization stress induced catecholamine biosynthetic enzymes gene expression, while ginseng appeared to restore homeostasis via suppression of TH and DBH gene expression. In part, the regulatory activity in the TH and DBH gene expression of ginseng may account for the anti-stress action produced by ginseng.