• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.29-34
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• 1999

The hyperactivity of cholinergic system in the RVLM of spontaneously hypertensive rats (SHR) may contribute to the sustained elevation of blood pressure. However, the hyperactivity mechanisms of cholinergic system are controversial. Thus, to clarify the mechanisms of cholinergic hyperactivity in RVLM of the SHR, we studied the activities of enzymes that participate in the biosynthesis and degradation of acetylcholine (ACh) and the density of muscarinic receptors in RVLM of the 14- to 18-week-old SHR and age-marched Wistar Kyoto rats (WKY). Choline acetyltransferase activity was far greater in RVLM of SHR than that of WKY. $[^3H]ACh$ release from RVLM was also greater in SHR than in WKY. Acetylcholinesterase activity and $[^3H]NMS$ binding of RVLM slice of SHR were not significantly different from that of WKY. These results suggest that the enhanced cholinergic mechanisms in the RVLM of SHR is due to the enhanced presynaptic cholinergic tone rather than the altered postsynaptic mechanisms.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.28 no.4
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• pp.29-40
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• 2015

Objects : The aim of this study is to introduce latest research trend of cholinergic urticaria and consider results in view of Korean medicine.Methods : We investigate research papers, Chinese and Korean medicinal papers about Cholinergic Urticaria through Pubmed, CNKI(China National Knowledge Infrastructure) and OASIS(Oriental Medicine Advanced Searching Integrated System).Results : The pathogenesis of cholinergic urticaria is supposed to correlate with sweating, considering that many cholinergic urticaria patients are complicated with anhidrosis or hypohidrosis and have sweat hypersensitivity. And on the basis of those outcomes, diverse therapies on cholinergic urticaria are conducted recently.Conclusion : Korean medicinal approaches and treatment on cholinergic urticaria can be significant, accounting that sweating plays a important role in pathogenesis of cholinergic urticaria.

• Molecules and Cells
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• v.38 no.9
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• pp.796-805
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• 2015

Gintonin is a novel ginseng-derived lysophosphatidic acid (LPA) receptor ligand. Oral administration of gintonin ameliorates learning and memory dysfunctions in Alzheimer's disease (AD) animal models. The brain cholinergic system plays a key role in cognitive functions. The brains of AD patients show a reduction in acetylcholine concentration caused by cholinergic system impairments. However, little is known about the role of LPA in the cholinergic system. In this study, we used gintonin to investigate the effect of LPA receptor activation on the cholinergic system in vitro and in vivo using wild-type and AD animal models. Gintonin induced $[Ca^{2+}]_i $ transient in cultured mouse hippocampal neural progenitor cells (NPCs). Gintonin-mediated $[Ca^{2+}]_i $ transients were linked to stimulation of acetylcholine release through LPA receptor activation. Oral administration of gintonin-enriched fraction (25, 50, or 100 mg/kg, 3 weeks) significantly attenuated scopolamine-induced memory impairment. Oral administration of gintonin (25 or 50 mg/kg, 1 2 weeks) also significantly attenuated amyloid-${\beta}$ protein ($A{\beta}$)-induced cholinergic dysfunctions, such as decreased acetylcholine concentration, decreased choline acetyltransferase (ChAT) activity and immunoreactivity, and increased acetylcholine esterase (AChE) activity. In a transgenic AD mouse model, long-term oral administration of gintonin (25 or 50 mg/kg, 3 months) also attenuated AD-related cholinergic impairments. In this study, we showed that activation of G protein-coupled LPA receptors by gintonin is coupled to the regulation of cholinergic functions. Furthermore, this study showed that gintonin could be a novel agent for the restoration of cholinergic system damages due to $A{\beta}$ and could be utilized for AD prevention or therapy.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.2
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• pp.185-192
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• 1998

A role of endogenous somatostatin in pancreatic exocrine secretion induced by intrapancreatic cholinergic activation was studied in the isolated rat pancreas perfused with modified Krebs-Henseleit solution. Intrapancreatic neurons were activated by electrical field stimulation (EFS: 15 V, 2 msec and 8 Hz). Pancreatic exocrine secretion, including volume flow and amylase output, and release of somatostatin from the pancreas were respectively determined. Somatostatin cells in the islet were stained with an immunoperoxidase method. EFS significantly increased pancreatic volume flow and amylase output, which were reduced by atropine by 59% and 78%, respectively. Intraarterial infusion of either pertussis toxin or a somatostatin antagonist resulted in a further increase in the EFS-evoked pancreatic secretion. EFS also further elevated exocrine secretion in the pancreas treated with cysteamine, which was completely restored by intraarterial infusion of somatostatin. EFS significantly increased not only the number of immunoreactive somatostatin cells in the islet but also the concentration of immunoreactive somatostatin in portal effluent. It is concluded from the above results that intrapancreatic cholinergic activation elevates pancreatic exocrine secretion as well as release of endogenous somatostatin. Endogenous somatostatin exerts an inhibitory influence on exocrine secretion induced by intrapancreatic cholinergic activation via the islet-acinar portal system in the isolated pancreas of the rat.

• Archives of Craniofacial Surgery
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• v.22 no.1
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• pp.1-10
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• 2021

Botulinum toxin type A (BoNT-A), onabotulinumtoxinA (Botox) was approved by the United States Food and Drug Administration for temporary improvement of glabellar lines in patients 65 years and younger in 2002, and has also been used widely for aesthetic purposes such as hyperhidrosis, body shape contouring, and other noninvasive facial procedures. BoNT-A inhibits presynaptic exocytosis of acetylcholine (ACh)-containing vesicles into the neuromuscular junction at cholinergic nerve endings of the peripheral nervous system, thereby paralyzing skeletal muscles. ACh is the most broadly used neurotransmitter in the somatic nervous system, preganglionic and postganglionic fibers of parasympathetic nerves, and preganglionic fibers or postganglionic sudomotor nerves of sympathetic nerves. The scientific basis for using BoNT-A in various cosmetic procedures is that its function goes beyond the dual role of muscle paralysis and neuromodulation by inhibiting the secretion of ACh. Although the major target organs for aesthetic procedures are facial expression muscles, skeletal body muscles, salivary glands, and sweat glands, which are innervated by the somatic or autonomic nerves of the peripheral cholinergic nerve system, few studies have attempted to directly explain the anatomy of the areas targeted for injection by addressing the neural physiology and rationale for specific aesthetic applications of BoNT-A therapy. In this article, we classify the various cosmetic uses of BoNT-A according to the relevant component of the peripheral nervous system, and describe scientific theories regarding the anatomy and physiology of the cholinergic nervous system. We also review critical physiological factors and conditions influencing the efficacy of BoNT-A for the rational aesthetic use of BoNT-A. We hope that this comprehensive review helps promote management policies to support long-term, safe, successful practice. Furthermore, based on this, we look forward to developing and expanding new advanced indications for the aesthetic use of BoNT-A in the future.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.113-121
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• 1998

To clarify whether nizatidine, a $H_2$ receptor antagonist, has the cholinergic activity, the effects of nizatidine on the guinea pig ileum and on the acetylcholinesterase in human serum were studied. And, the mechanism of excitatory effect of nizatidine on the cholinergic system in ileum was also studied. Nizatidine caused a concentration-dependent contractile response by the guinea pig ileum. The $EC_{50}\;was\;53\;{\mu}M$ and the maximum response was at $300\;{\mu}M$. Ranitidine also caused a contractile response by the guinea pig ileum, but cimetidine and famotidine did not. The pretreatment with $H_1$ receptor antagonist did not affect the actions of nizatidine on the guinea pig ileum, but the pretreatment with atropine completely blocked them. Nizatidine significantly enhanced the acetylcholine-induced response of the guinea pig ileum, but not the pilocarpine-induced response. Nizatidine did not affect the histamine-induced response of the guinea pig ileum. Nizatidine still exerted the small excitatory effect on the guinea pig ileum pretreated with the high concentration of physostigmine. Nizatidine significantly inhibited the acetylcholinesterase in human serum. These results suggest that nizatidine exerts an excitatory effect on guinea pig ileum which seems to be associated with the cholinergic system, probably through an indirect mechanism, inhibition of acetylcholinesterase and/or increased release of acetylcholine.

• The Journal of Korean Medicine
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• v.23 no.2
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• pp.125-138
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• 2002

Learning and memory are essential requirements for every living organism in order to cope with environmental demands, and cholinergic systems are known to be involved in learning and memory. Scutellaria baicalensis (SB) and Gastrodia elata (GE) as a traditional Oriental medicine have been clinically used to treat or prevent memory deficits, including Alzheimer's disease. In the present study, we investigated the effects of SB and GE on learning and memory in the Morris water maze task and the central cholinergic system of the rats with excitotoxic medial septum lesions. In the water maze test, the animals were trained to find a platform at a fixed position over 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the medial septum (MS) impaired their performance in the maze test (latency of acquisition test on the 3rd day, $27.6{\pm}$4.4 sec vs. $61.7{\pm}17.7$ sec; retention test, $7.9{\pm}1.3%$ vs. $5.7{\pm}1.0%$: sharn vs. ibotenic lesioned groups, respectively) and reduced choline acetyltransferase (ChAT) - immunoreactivity in the MS and the hippocarnpus, which is a marker for degeneration of the central cholinergic system (number of cells, $21.1{\pm}1.1$ vs. $13.2{\pm}1.3$: sham vs. ibotenic lesioned group). Daily administrations of SB (100mg/kg, p.o.) and GE (100mg/kg, p.o.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the MS and the hippocarnpus induced by ibotenic acid. These results demonstrated that SB and GE ameliorated learning and memory deficits through effects on the central nervous system, partly through effect on the acetylcholine system. Our studies suggest an evidence of SB and GE as treatment for Alzheimer's disease.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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• pp.28-34
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• 1993

Using in vitro autoradiography with a digital autoradiography system and radioreceptor assay, the distribution and the binding characteristics of the muscarinic cholinergic receptors (mAChR) were studied in regions of rat brain. Radioreceptor assay revealed that mAChR could be measured with saturation binding assay in the brain and heart homogenates: No difference in Kd or Bmax of the brain or heart was found between the normal Wistar rats and SHR rats. Specific binding of $^3H$ quinuclidinyl benzilate (QNB) increased and saturation was reached by 2 hours after incubation with slide-mounted brain tissue. The distribution of mAChR was heterogeneous along the fields of brain. Affinity (Kd) of mAChR was not different significantly among cortex, hippocampus and caudate-putamen. No difference was found between normal rats and SHR strain. More receptors (Bmax) were found in the cortex and hippocampus than in the caudate-putamen in normal rats. More receptors were found in the cortex and caudate-putamen in SHR rats than in normal rats. Radioreceptor assay and digital autoradiographic analysis of affinity and number of mAChR gave the same results. With the above findings, we concluded that we could use digital autoradiographic system with $^3H$-QNB in the characterization of mAChR of rats and that the cortex and caudate-putamen of SHR strain rats have more receptors than those of normal rats.

• The Journal of Korean Medicine
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• v.29 no.5
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• pp.67-76
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• 2008

Objectives : Amnesia is theloss or impairment of memory, caused by physical injury, disease, drugs, or emotional trauma. Recently, the average life span is increasing, while at the same time, the incidence of dementia-like diseases in conjunction with amnesia are also increasing. Therefore learning and memory are very important issues in modern society. Ancient Korean physicians used several herbs to treat dementia and these herbal effects were described in Korean herbal books. Among them are some reports on several cognitive-enhancing herbs which have since been shown to improve dementia in recent pharmacological studies, such as Panax ginseng; however, the facilitatory effects of many Korean cognitive-enhancing herbs on learning and memory are limited. Learning and memory are essential requirements for every living organism in order to cope with environmental demands; cholinergic systems are known to be involved in learning and memory. Methods : In this study, the effects of Acori graminei rhizoma (AGR, 石菖蒲) on learning and memory were investigated by Morris water maze, eight-arm radial maze, and the effects on the central cholinergic system of rats injected with scopolamine. Results : In the water maze, the experimental animals were trained to find a platform in a fixed position for 6 days and then received a 60 sec probe trial in which the platform was removed from the pool on the 7th day. In the eight-arm radial maze, the animals were tested four times per day for 6 days. Scopolamine impaired performance of the maze tests and reduced activity of acetylcholinesterase (AchE) in the hippocampus, which is a marker for the central cholinergic system. There were significant reversals from the scopolamine-induced deficits on learning and memory in these tests, through daily administrations of AGR (100 mg/kg, p.o.) over 14 consecutive days. These treatments also reduced the loss of cholinergic activity in the hippocampus induced by scopolamine. Conclusions : These results demonstrated that AGR ameliorated learning and memory deficits by affecting the central acetylcholine system.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.63-70
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• 2002

Cholinergic modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) by the activation of muscarine receptors was investigated in mechanically dissociated rat nucleus basalis of the Meynert neurons using the conventional whole-cell patch recording configuration. Muscarine $(10{\mu}M)$ reversibly and concentration-dependently decreased mIPSC frequency without affecting the current amplitude distribution. Muscarine action on GABAergic mIPSCs was completely blocked by $1{\mu}M$ methoctramine, a selective $M_2$ receptor antagonist, but not by $1{\mu}M$ pirenzepine, a selective $M_1$ receptor antagonist. NEM $(10{\mu}M),$ a G-protein uncoupler, attenuated the inhibitory action of muscarine on GABAergic mIPSC frequency. Muscarine still could decrease GABAergic mIPSC frequency even in the $Ca^{2+}-free$ external solution. However, the inhibitory action of muscarine on GABAergic mIPSCs was completely occluded in the presence of forskolin. The results suggest that muscarine acts presynaptically and reduces the probability of spontaneous GABA release, and that such muscarine-induced inhibitory action seems to be mediated by G-protein-coupled $M_2$ receptors, via the reduction of cAMP production. Accordingly, $M_2$ receptor-mediated disinhibition of nBM neurons might play one of important roles in the regulation of cholinergic outputs from nBM neurons as well as the excitability of nBM neurons themselves.