• YAKHAK HOEJI
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• v.32 no.6
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• pp.428-434
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• 1988

The effects of calcium and calcium antagonist, nifedipine on the adrenergic receptor-stimulated glycogenolysis were investigated in isolated rat hepatocytes. The hepatic glycogenolysis induced by alpha-adrenergic receptor stimulation depended on calcium ions, and beta-adrenergic activation was unrelated to calcium ions. Nifedipine decreased the alpha-adrenergic agonist-induced glucose release significantly and the decrease was depended on calcium ions. The glucose release induced by beta-adrenergic agonist was not inhibited by nifedipine.

• Korean Journal of Clinical Pharmacy
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• v.34 no.1
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• pp.1-20
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• 2024

This review examines the pivotal clinical trials that evaluated the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the management of obesity. The reported findings underscore significant and sustained weight loss achieved with semaglutide in diverse patient groups, although gastrointestinal disorders occurred frequently, leading to therapy discontinuation. Overall, the studies demonstrated the potential of semaglutide as a therapeutic option not only for type 2 diabetes but also for obesity. The treatment landscape in obesity is evolving, as reflected in changing regulatory approvals and clinical guidelines, suggesting a paradigm shift toward personalized approaches in this chronic disease states to achieve optimal treatment outcomes for patients.

• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.405-414
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• 2003

The purpose of this study was to assess the role of tachykinins (TK) in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the longitudinal muscle of the rat ileum. In the presence of atropine ($1{\mu}M$), guanethidine ($5{\mu}M$), and L-nitroarginine (L-NNA, $200{\mu}M$), EFS (0.5ms pulse duration, 120 V, 1-20 Hz for 2 min) produced a frequency-dependent slowly-developing tonic contraction with superimposed phasic contractions ('on'-contraction) followed by off slowly-decreasing tonic and superimposed phasic contractions ('off'-contraction) of mucosa-free longitudinal oriented muscle strip. These EFS induced responses were blocked by tetrotoxin. $NK_1$ receptor selective antagonist L-732,138 strongly inhibited the EFS-induced excitatory responses. However $NK_2$ receptor selective antagonist, GR 159897 and $NK_3$ receptor selective antagonist SB 222200 did not significantly inhibited the responses. $NK_1$ receptor selective agonist [$Sar^9$,$Met(O_2)^{11}$] Substance P and $NK_2$ receptor selective agonist [${\beta}-Ala^8$]-neurokinin A (4-10) induced tonic contraction with superimposed phasic contractions of longitudinal oriented muscle strip and almost blocked by selective antagonist L-732,138 and GR 159897, respectively. But $NK_3$ receptor selective agonist senktide did not showed any effect. Nifedipine ($1{\mu}M$) abolished the contraction produced either by EFS or by the TK receptor agonists [$Sar^9$,$Met(O_2)^{11}$] Substance P or [${\beta}-Ala^8$]-neurokinin A (4-10). It is concluded that, in the longitudinal muscle of rat ileum, both $NK_1$ and $NK_2$ receptors modulated the responses to exogenous tachykinins, whereas $NK_1$ is mainly involved in NANC neuromuscular contraction.

• Journal of Life Science
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• v.19 no.11
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• pp.1506-1513
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• 2009

RGS proteins have been identified as negative regulators of G protein signalling pathways and attenuate the activity of GPCR receptors. However, information on the regulatory effects of RGS proteins in the activity of cannabinoid receptors is limited. In this study, the role of RGS proteins on the signal transduction of the CB2 cannabinoid receptor was investigated in HEK293 cells co-transfected with CB2-receptors and plasmids encoding RGS2, RGS3, RGS4 and RGS5. Treatment of cells with WIN55, 212-2, a CB2 receptor agonist, inhibited forskolin-induced cAMP response element (CRE) activity in CB2-transfected HEK293 (CB2-HEK293) cells. This inhibitory effect of WIN 55, 212-2 on CRE activity was reversed by co-transfection of CB2-HEK293 cells with RGS3, but not with RGS2, RGS4 and RGS5. However, endogenous RGS3 protein knocked down by a small interfering siRNA targeting RGS3 gene enhanced inhibition of forskolin induced CRE activity via agonist induced CB2 receptor signal transduction. These results indicate the functional role of endogenous RGS protein in cannabinoid signaling pathways and define receptor-selective roles of endogenous RGS3 in modulating CRE transcriptional responses to agonist induced CB2 receptor activity.

• Proceedings of the PSK Conference
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• 2001.04a
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• pp.122.3-123
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• 2001

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.5
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• pp.263-268
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• 2005

Striatum has important roles in motor control, habitual learning and memory. It receives glutamatergic inputs from neocortex and thalamus, and dopaminergic inputs from substantia nigra. We examined effects of dopamine (DA) on the corticostriatal synaptic transmission using in vitro extracellular recording technique in rat brain corticostriatal slices. Synaptic responses were elicited by stimulation of cortical glutamatergic inputs on the corpus callosum and recorded in the dorsal striatum. Corticostriatal population spike (PS) amplitudes were decreased ($39.4{\pm}7.9$%) by the application of $100{\mu}M$ DA. We applied receptor subtype specific agonists and antagonists and characterized the modulation of corticostriatal synaptic transmission by different DA receptor subtypes. $D_2$ receptor agonist (quinpirole), antagonist (sulpiride), and $D_1$ receptor antagonist (SKF 83566), but not $D_1$ receptor agonist (SKF 38393), induced significantly the reduction of striatal PS. Pretreatment neither with SKF 83566 nor sulpiride significantly affected corticostriatal synaptic inhibition by DA. However, the inhibition of DA was completely blocked by pretreatment with mixed solution of both SKF 83566 and sulpiride. These results suggest that DA inhibits corticostriatal synaptic transmission through both $D_1$ and $D_2$ receptors in concert with each other.

• Bulletin of the Korean Chemical Society
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• v.33 no.5
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• pp.1475-1479
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• 2012

Human peroxisome proliferator-activated receptor gamma ($hPPAR{\gamma}$) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. In this study, we verified that amentoflavone is an agonist of $hPPAR{\gamma}$ and probed the molecular basis of its action. It was demonstrated that amentoflavone bound $hPPAR{\gamma}$ with high (picomolar) affinity and increased the binding between $hPPAR{\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 4-fold. Based on a docking study, for the first time, we propose a model of amentoflavone and $hPPAR{\gamma}$ binding in which amentoflavone forms three hydrogen bonds with the side chains of His323, Tyr327, and Arg280 in $hPPAR{\gamma}$ and participates in two hydrophobic interactions.

• Annals of Pediatric Endocrinology and Metabolism
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• v.22 no.1
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• pp.15-26
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• 2017

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Patients with T2D suffer from various diabetes-related complications. Since there are many patients with T2D that cannot be controlled by previously developed drugs, it has been necessary to develop new drugs, one of which is a glucagon-like peptide-1 (GLP-1) based therapy. GLP-1 has been shown to ameliorate diabetes-related conditions by augmenting pancreatic ${\beta}-cell$ insulin secretion and having the low risk of causing hypoglycemia. Because of a very short half-life of GLP-1, many researches have been focused on the development of GLP-1 receptor (GLP-1R) agonists with long half-lives such as exenatide and dulaglutide. Now GLP-1R agonists have a variety of dosing-cycle forms to meet the needs of various patients. In this article, we review the physiological features of GLP-1, the effects of GLP-1 on T2D, the features of several GLP-1R agonists, and the therapeutic effect on T2D.

• International Journal of Oral Biology
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• v.34 no.4
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• pp.215-222
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• 2009

Medial vestibular nucleus (MVN) neurons are involved in the reflex control of the head and eyes, and in the recovery of vestibular function after the formation of peripheral vestibular lesions. In our present study, whole cell patch clamp recordings were carried out on MVN neurons in brainstem slices from neonatal rats to investigate the actions of a group I metabotropic glutamate receptor (mGluR) agonist upon synaptic transmission and ionic currents. Application of the mGluR I agonist (S)-3,5- dihydroxyphenylglycine (DHPG) increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs) but had no effect upon amplitude distributions. To then identify which of mGluR subtypes is responsible for the actions of DHPG in the MVN, we employed two novel subtype selective antagonists. (S)-(+)-$\alpha$-amino-a-methylbenzeneacetic acid (LY367385) is a potent competitive antagonist that is selective for mGluR1, whereas 2-methyl-6-(phenylethynyl)-pyridine (MPEP) is a potent noncompetitive antagonist of mGluR5. Both LY367385 and MPEP antagonized the DHPG-induced increase of mIPSCs, with the former being more potent. DHPG was also found to induce an inward current, which can be enhanced under depolarized conditions. This DHPG-induced current was reduced by both LY367385 and MPEP. The DHPG-induced inward current was also suppressed by the PLC blocker U-73122, the $IP_3$ receptor antagonist 2-APB, and following the depletion of the intracellular $Ca^{2+}$ pool by thapsigargin. These data suggest that the DHPG-induced inward current may be mainly regulated by the intracellular $Ca^{2+}$ store via the PLC-$IP_3$ pathway. In conclusion, mGluR I, via pre- and postsynaptic actions, may modulate the excitability of the MVN neurons.

• Bulletin of the Korean Chemical Society
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• v.32 no.8
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• pp.2717-2721
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• 2011

Peroxisome proliferator-activated receptors (PPARs) are a subfamily of nuclear receptors (NRs). Human peroxisome proliferator-activated receptor gamma (hPPAR${\gamma}$) has been implicated in the pathology of numerous diseases, including obesity, diabetes, and cancer. ELISA-based hPPAR${\gamma}$ activation assay showed that biapigenin increased the binding between hPPAR${\gamma}$ and steroid receptor coactivator-1 (SRC-1) by approximately 3-fold. In order to confirm that biapigenin binds to hPPAR${\gamma}$, fluorescence quenching experiment was performed. The results showed that biapigenin has higher binding affinity to hPPAR${\gamma}$ at nanomolar concentrations compared to indomethacin. Biapigenin showed anticancer activity against HeLa cells. Biapigenin was noncytotoxic against HaCa T cell. All these data implied that biapigenin may be a potent agonist of hPPAR${\gamma}$ with anticancer activity. We will further investigate its anticancer effects against human cervical cancer.