• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.547-554
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• 2018

Itching is a common clinical symptom of skin disease that significantly affects a patient's quality of life. Transient receptor potential vanilloid 1 (TRPV1) receptors of keratinocytes and peripheral nerve fibers in skin are involved in the regulation of itching as well as pain. In this study, we investigated whether curcumin, which acts on TRPV1 receptors, affects histamine-induced itching in mice, using behavioral tests and electrophysiological approaches. We found that histamine-induced itching was blocked by topical application of curcumin in a concentration-dependent manner. In ex-vivo recordings, histamine-induced discharges of peripheral nerves were reduced by the application of curcumin, indicating that curcumin acts directly on peripheral nerves. Additionally, curcumin blocked the histamine-induced inward current via activation of TRPV1 (curcumin $IC_{50}=523nM$). However, it did not alter chloroquine-induced itching behavior in mice, which is associated with transient receptor potential ankyrin 1 (TRPA1). Taken together, our results suggest that histamine-induced itching can be blocked by topical application of curcumin through the inhibitory action of curcumin on TRPV1 receptors in peripheral nerves.

• Molecules and Cells
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• v.28 no.4
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• pp.365-368
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens and initiating innate immune responses. The stimulation of TLRs by microbial components triggers the activation of myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-${\beta}$ (TRIF)-dependent downstream signaling pathways. Isoliquiritigenin (ILG), an active ingredient of Licorice, has been used for centuries to treat many chronic diseases. ILG inhibits the MyD88-dependent pathway by inhibiting the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether ILG inhibits the TRIF-dependent pathway. To evaluate the therapeutic potential of ILG, we examined its effect on signal transduction via the TRIF-dependent pathway of TLRs induced by several agonists. ILG inhibited nuclear factor-${\kappa}B$ and interferon regulatory factor 3 activation induced by lipopolysaccharide or polyinosinic-polycytidylic acid. ILG inhibited the lipopolysaccharide-induced phosphorylation of interferon regulatory factor 3 as well as interferon-inducible genes such as interferon inducible protein-10, and regulated activation of normal T-cell expressed and secreted (RANTES). These results suggest that ILG can modulate TRIF-dependent signaling pathways of TLRs, leading to decreased inflammatory gene expression.

• Journal of Pharmacopuncture
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• v.23 no.1
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• pp.1-7
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• 2020

Nicotine, primary component of tobaco produces craving and withdrawal effect both in humans and animals. Nicotine shows a close resemblance to other addictive drugs in molecular, neuroanatomical and pharmacological, particularly the drugs which enhances the cognitive functions. Nicotine mainly shows its action through specific nicotinic acetylcholine receptors located in brain. It stimulates presynaptic acetylcholine receptors thereby enhancing Ach release and metabolism. Dopaminergic system is also stimulated by it, thus increasing the concentration of dopamine in nuclear accumbens. This property of nicotine according to various researchers is responsible for reinforcing behavioral change and dependence of nicotine. Various researchers have also depicted that some non dopaminergic systems are also involved for rewarding effect of nicotinic withdrawal. Neurological systems such as GABAergic, serotonergic, noradrenergic, and brain stem cholinergic may also be involved to mediate the actions of nicotine. Further, the neurobiological pathway to nicotine dependence might perhaps be appropriate to the attachment of nicotine to nicotinic acetylcholine receptors, peruse by stimulation of dopaminergic system and activation of general pharmacological changes that might be responsible for nicotine addiction. It is also suggested that MAO A and B both are restrained by nicotine. This enzyme helps in degradation dopamine, which is mainly responsible for nicotinic actions and dependence. Various questions remain uninsurable to nicotine mechanism and require more research. Also, various genetic methods united with modern instrumental analysis might result for more authentic information for nicotine addiction.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.59-59
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• 2003

Serotonin (5-HT; 5-hydroxytryptamine) exerts multiple effects on central nervous system as well as behaviors such as mood and appetite. The signaling of serotonin is mediated by 7 families of serotonin receptors, designated 5-HT$_1$ to 5-HT$_{7}$. Six families of this receptor are G-protein coupled 7TM receptors, and the third intracellular loop of these receptors is proposed to interact with specific types of G-proteins. To investigate the specific interaction between the third intracellular loop of 5-HT$_{6}$ with G$\square$s, we have constructed a chimera protein that represent the third intracellular loop of 5-HT$_{6}$ within a leucine zipper motifs, In addition an alpha subunit of human G-protein that interact with 5-HT$_{6}$ was cloned into a bacterial expression vector. The two proteins were expressed in E. coli and purified in homogeneity. The interaction of the prepared proteins was examined by ELISA assay. The affinity between the two proteins and effect of insertion mutations were discussed.ussed.d.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.40-40
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• 2003

Spontaneous firing rate and patterns of dopaminergic neurons in midbrain are key factors in determining the level of dopamine at target loci as well as in the mechanisms such as reward and motor coordination. Although glutamate, as a major afferent, is reported to enhance firing rate, the detailed actions of NMDA-, AMPA/kainate-, and metabotropic glutamate receptors (mGluR) on filing patterns are not clear. Thus we have investigated the role of glutamate receptors on the spontaneous firing activities using the network-free, acutely isolated dopamine neurons from substantia nigra pars compacta(SNc) of the 9-14 days rat. The isolated cells showed spontaneous regular firings of near 2.5 Hz, whose rate was enhanced by glutamate at submicromolar levels (0.3 $\square$M) but abolished by high concentrations more than 10 $\square$M.

• Archives of Pharmacal Research
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• v.26 no.1
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.

• Bulletin of the Korean Chemical Society
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• v.30 no.12
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• pp.2938-2942
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• 2009

New receptors 1-3 that bind stereoselectively amino alcohols and convert chirality of amino acidsvia imine bond formation were synthesized. The receptors have uryl (1), thiouryl (2) and guanidinium (3) groups all with additional phenylcarbonyl motifs, which are effective hydrogen bonding donors and play a key role in the stereoselective recognitions. The stereoselectivities were measured from the integration of $^1HNMR$ peaks. Compound 1 and 2 showed the stereoselectivities for the imine formation with amino alcohols ($K_R/K_S$) in the range of 2${\sim}$4, and compound 3 in the range of 4${\sim}$8. Chirality conversion efficienciesof 1-3 for amino acids, i.e. D/L ratio at equilibrium, are in the range of 1.5${\sim}$5.6, showing a little higher efficiency with 3. The additional phenylcarbonyl motifs in 1-3 were revealed not to contribute to significant enhancement of the selectivities.

• BMB Reports
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• v.29 no.6
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• pp.525-529
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• 1996

Ligand binding properties of muscarinic acetylcholine receptors (mAChRs) in the nematode Caenorhabditis elegans (C. elegans) were characterized by using filtration binding assays. Scatchard analysis using $[^{3}H]N-methylscopolamine$ ($[^{3}H]NMS$) showed that the dissociation constant ($K_d$) and the maximum binding value ($B_{max}$) were $3.3{\pm}0.8{\times}10^{10}$ M and $9.0{\pm}1.1$ fmol/mg protein, respectively. Binding competition experiments indicated that the affinities of C. elegans mAChRs to atropine, scopolamine, and oxotremorine were similar to those of mammalian mAChRs. Pirenzepine binding experiments revealed that the binding pattern of mAChRs in C. elegans closely resembled that of mAChRs in rat brain, suggesting that the receptors consist primarily of Ml subtype. The affinity of mAChRs for oxotrernorine was significantly affected by guanylylimidodiphosphate (Gpp(NH)p), a non hydrolyzable GTP analog, suggesting that mAChRs in C. elegans might be coupled to G proteins. The data presented here indicate the possibility that C. elegans provides a living animal model to study the action mode of the muscarinic cholinergic system.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.394-400
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• 1991

A question whether abnormal responsiveness of hypothalamic catecholaminergic nervous system to ovarian steoid hormones in spontaneously hypertensive rats (SHR) exist was investigated. Four groups of experimental animals were prepared for SHR and normotensive Wistar rats (NW) respectively: 1) intact, 2) ovariectomized (OVX+V), 3) ovariectomized and estrogen treated (OVX+E), 4) ovariectomized and estrogen plus progesterone treated (OVX+E+P) groups. Hypothalami from experimental animals were dissected out and used for determination of .alpha.-adrenergic receptor binding characteristics and catecholamine contents. Norepinephrine(NE) content and B$_{max}$ of $\alpha_1$-adrenergic receptors in hypothalami were greater in intact SHR than in intact NW, but dopamine(DA) content was lower in SHR than in NW. Neither contents of NE and DA nor binding characteristics of $\alpha_1$-adrenergic receptors were different in OVX+V and OVX+E group from intact group of both SHR and NW. Kd and B$_{max}$ of $\alpha_1$-adrenergic receptors in OVX+E+P was lower than that in intact SHR but not in NW. DA content was lower in OVX+E+P than in intact group of SHR and NW. The result of the present study indicates that there is an abnormal responsiveness of hypothalamic catecholaminergic nervous system to ovarian steroid hormones in SHR which may be one of genetically-determined factors probably not responsible for the development of hypertension.

• Archives of Pharmacal Research
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• v.22 no.1
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• pp.1-8
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• 1999

Transforming growth factor-$\beta$ (TGF-$\beta$) is the prototypical multifunctional cytokine, participating in the regulation of vital cellular activities such as proliferation and differentiations as well as a number of basic physiological functions. The effects of TGF-$\beta$ are critically dependent on the expression and distribution of a family of TGF-$\beta$ receptors, the TGF-$\beta$ types I, II, and III. It is now known that a wide variety of human pathology can be caused by aberrant expression and function of these receptors. the coding sequence of the type II receptor (RII) appears to render it uniquely susceptible to DNA replication errors in the course of normal cell division. By virtue of its key role in the regulation of cell proliferation, TGF-$\beta$ RII should be considered as a tumor suppressor gene. High levels of mutation in the TGF-$\beta$ RII gene have been observed in a wide range of primarily epithelial malignancies, including colon and gastric cancer. It appears likely that mutation of the TGF-$\beta$ RII gene may be a very critical step in the pathway of carcinogenesis.