• 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.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.21-31
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• 1991

When administered intracerebroventricularly (icv), cholinergic nicotinic agents, nicotine and DMPP, as well as cholinergic muscarinic agents, muscarine and bethanechol, produced pressor responses in urethane-anesthetized vagotomized rabbits. The response patterns to nicotine and to DMPP were similar, while the bethanechol response resembled the muscarine pattern. The pressor response to nicotine and DMPP was markedly inhibited by icv mecamylamine but not by icv pirenzepine, whereas the response to muscarine and bethanechol was inhibited by icv pirenzepine but not by icv mecamylamine, suggesting that both nicotinic and muscarinic receptors in the brain are involved in the action. Intravenous pretreatments of animals with regitine, reserpine, enalapril, saralasin, both regitine and enalapril, both regitine and saralasin, SK&F-100273 did not prevent the pressor response to nicotine and muscarine. Iv pretreatments with both regitine and SK&F-100273 inhibited the nicotine response without affecting the muscarine response, whereas pretreatments with three agents, regitine, enalapril and SK&F-100273, inhibited the muscarine response. The nicotine-induced elevated blood pressure as well as the muscarine-induced were lowered by regitine but not by enalapril or by SK&F-100273. Enalapril was without effect on the nicotine hypertension in rabbits treated with regitine or both regitine and SK&F-100273, whereas SK&F-100273 lowered the nicotine hypertension in regitine-treated animals. Enalapril did not enhance the lowering effect of SK&F-100273 in regitine-treated ones, nor did it cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and SK&F-100273. Likewise, SK&F-100273 did not cause a fall of the muscarine hypertension induced in regitine-treated rabbits, but it did lower the blood pressure in animals treated with both regitine and enalapril. These data suggest that the nicotine-induced hypertensive state is related to at least two systems in the periphery-sympathetic and vasopressin, whereas in the muscarine-induced hypertensive state three systems in the periphery are involved, i.e., the sympathetic, vasopressin and angiotensin system. The hypotensive effect of regitine on basal arterial blood pressure levels of rabbits was not influenced by pretreatment with either of enalapril or SK&F-100273, but significantly potentiated by treating with both enalapril and SK&F-100273, suggesting participation of the sympathetic and the renin-angiotensin system as well as the vasopressin system in maintenance of arterial blood pressure.

• Toxicological Research
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• v.2 no.2
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• pp.51-62
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• 1986

Of mushrooms found in Japan, approximately 35 species are classified as poisonous mushrooms. The mushroom poisonings caused by these mushrooms are classified as three types accodring to the symptoms and their toxic constitutents. The first type is the cholera-like symptom which is induced mainly by the toxic constitutents such as cyclopeptide and gyromitrin. The second type is the neurological mainfestations induced by muscarine (cholinergic), muscimol (delirium), psilocybin (hallucinogenic) and coprine (antabuse-like).

• The Korean Journal of Mycology
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• v.49 no.2
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• pp.139-153
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• 2021

The Inocybaceae is a family of ectomycorrhizal fungi belonging to the Agaricales order. Most species in this family produce secondary metabolites, such as muscarine, psilocybin, and other compounds. In the present study, we conducted taxonomic studies on the Inocybaceae based on morphological and molecular phylogenetic analyses for the first time in Korea. As a result, seven species of Inocybaceae were newly recorded: Inocybe caroticolor, I. fuscidula, I. grammatoides, I. latibulosa, I. stellata, Inosperma shawarense, and Mallocybe malenconii. Among them, the genera Inosperma and Mallocybe were described for the first time in Korea. Relevant morphological characteristics, phylogenetic trees, and photographs are provided.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.40-46
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• 1998

We investigated the influence of the root of Panax ginseng C. A. Meyer on the secretion of catecholamines from bovine adrenal chromaffin cells, which are used as a model of nervous systems. In two major parts extracted from the ginseng root, the crude saponin fraction, but not the non-saponin fraction, reduced the secretion from the cells, stimulated by acetylcholine (ACh). Ginseng saponins (ginsenosides) are classified into three groups, the panaxadiol, the panaxatriol and the oleanolic acid groups, on the basis of the chemical structures of their saponins. Both the panaxadiol and the panaxatriol saponins, excluding only one oleanolic acid saponin ginsenoside-Ro, generally reduced the ACh-evoked secretion. The inhibitory effects of the panaxatriol were much stronger than those of the panaxadiol. However, ginsenoside-Rg, and -Rh3 in the panaxadiol saponins were the potent inhibitors comparable to the panaxatriol saponins. Ginsenoside-Rg2 in the panaxatriol was the most effective. It is probable that the ginsenoside inhibition of the catecholamine secretion is due to the suppression of the function of the nicotinic ACh receptor-cation channels. On the other hand, ginsenoside-Rg2 did not affect the angiotensin II-, the bradykinin-, the histamine- and the neurotensin- induced catecholamine secretions from the chromaffin cells and the muscarine- and the histamine- induced contraction of the ileum in guinea-pigs. Ginsenoside-Rbl, a panaxadiol saponin, and ginsenoside-Ro had no or only a slight effect on them. On the contrary, ginsenoside-Rg3 not only competitively inhibited the muscarine-induced ileum contraction but also reduced the angiotensin R -, the bradykinin-, the histamine- and the neurotensin-induced catecholamine secretions. Thus, the ginseng root contains active ingredients, namely some ginsensides, which suppress the responses induced by receptor stimulation. The inhibitory effects of ginseng saponins may be one of the action mechanisms for the pharmacological effects of the Panax ginseng root.

• The Korean Journal of Physiology
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• v.26 no.2
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• pp.137-141
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• 1992

The present study was aimed at elucidating the mode of inhibitory action of tricyclic antidepressants on the smooth muscle. Effects of amitriptyline on the isolated detrusor muscle strips of the urinary bladder of the rabbit were examined. The spontaneous rhythmic movement of the muscle preparation was frequently observed, which was decreased or abolished by addition of amitriptyline $(10^{-5}{\sim}10^{-3}\;M)$. The muscle preparation responded with contraction dose dependently to carbachol, of which dose response curve shifted to the right in the presence of either amitriptyline or atropine. However, amitriptyline produced a nonparallel shift, whereas atropine caused a parallel one. In calcium free medium, the contraction response to carbachol was markedly decreased, which was resumed by the addition of $CaCl_2$ (2.5mM), but not in the presence of either amitriptyline or nifedipine. KCI (60 mM) produced a potent contraction, which was abolished in the presence of amitriptyline or nifedipine. These results suggest that amitriptyline, unlike atropine, not only acts as a noncompetitive antagonist at cholinergic muscarine receptors but also inhibits Ca-influx through the muscle cell membrane.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.192-198
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• 1995

The affinity of mequitazine, a non-sedating antihistamine, for muscarinic receptors was evaluated in the guinea-pig ventricle and ileum by in vitro binding techniques and functional studies. In binding studies, [$^3$H]quinuclidinyl benzilate (QNB) identified a single class of muscarinic receptors with similar apparent $K_{D}$ value of about 100 pM in two tissues. Mequitazine inhibited [$^3$H]QNB binding to muscarinic receptors competitively. Analysis of the mequitazine inhibition curve of [$^3$H]QNB binding to ventricular microsome and ileal homogenate indicated the presence of a single homogeneous binding site with Ki value of 25 nM and 18 nM, respectively. In functional studies, mequitazine caused parallel rightward shifts of concentration-response curves for carbachol and histamine in the isolated guinea-pig ileum. The slope values obtained from Schild plot analysis for the antagonistic action of mequitazine on muscarinic and histamine $H_1$-receptors were not significantly different from unity. The p $A_2$values of mequitazine for muscarinic and histamine $H_1$-receptors were about 7.6 ( $K_{M}$= 25.1 nM) and 8.88 ( $K_{H}$= 1.32 nM), respectively. These results indicate that the muscarinic receptor blocking action of mequitazine is 15 times less potent than the $H_1$receptor blocking action, but high concentration of this drug may cause the peripheral muscarinic receptor blocking effect.t.t.t.

• Biomolecules & Therapeutics
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• v.2 no.4
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• pp.361-368
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• 1994

The nature of the muscarinic receptors in bovine adrenal medulla was investigated in this study. [$^3$H]Quinuclidinyl benzilate(QNB) specifically bound to a single class of muscarinic receptor with a $K_{D}$ value of about 70 pM in bovine adrenal medullary, cardiac ventricular and ileal homogenates. Pirenzepine inhibition curves of [$^3$H]QNB binding to cardiac ventricular and ileal homogenates were steep, indicating the presence of a single class of binding site for pirenzepine with a Ki value of 990 nM and 508 nM, respectively. However, pirenzepine/[$^3$H]QNB competition binding curves in adrenal medulla suggested the presence of two binding sites (Hill coefficient=0.59) with a high( $M_1$) and a low( $M_2$) affinity. Respective Ki values for pirenfepine were 16 nM and 633 nM, with 44% of total sites having a high affinity( $M_1$). Gallamine, which is selective to cardiac $M_2$-receptor, inhibited [$^3$H]QNB binding to adrenal medullary, cardiac ventricular and ileal homogenates with Ki values of 12 $\mu$M, 6 $\mu$M and 13 $\mu$M, respectively. Thus, the binding affinities of pirenzepine and gallamine for $M_2$-receptor in adrenal medulla were similar to those in ileum, which contains the $M_3$-receptor. These results indicate that the $M_1$- and $M_3$- muscarinic receptor subtypes coexist in the bovine adrenal medulla.a.

• 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.

• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.236-254
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• 1996

This study was carried out to investigate the tracheal muscle relaxation of water extracts of three kinds of Coptis rhizoma and also compare their effects with berberine and palmatine, which are the important alkaloid components of Coptis rhizoma, in isolated rat tracheal smooth muscle. As a result Coptis chinenis showed significant tracheal muscle relaxation on KCI-induced contraction and more markedly on carbachol-induced contraction in dose-dependent manner. Coptis japoinin exhibited also tracheal muscle relaxation on both contraction with slightly weaker activities than those of Coptis chinensts. The activities of the root hair of Coptis chinensis were the most weakest in three rhizomas. Berberine and palmatine had strong tracheal muscle relaxation, especially, on carbachol-induced contraction, however, their activities on KCI-induced contraction were weaker than that of Coptis chinenis. The inhibitory effects of three kinds of Coptis rhizoma on the contraction by KCI and carbachol were investigated to explain the process of their tracheal muscle relaxation. All rhizomas inhibited the contraction by both agents, among them, Coptis japonica showed the most significant effect, so indicating that the tracheal muscle relaxation of Coptis rhizoma may be concerned with the blocking of muscarine receptor and $Ca^{2+}$channel.