• Proceedings of the Korean Society of Developmental Biology Conference
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• 2005.10a
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• pp.44-45
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• 2005

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2005.10a
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• pp.44-45
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• 2005

• 대한생식의학회:학술대회논문집
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• 2005.06a
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• pp.136.1-136.1
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• 2005

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.96-96
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• 2002

We examined the role of SR 144528 (N-[-(1S-endo-1,3,,3-trimethyl-bicycle[2, 2, 1 ] heptan-2-y1]-5-(-4-chloro-3-mothyl-phenyl)-(4-methylbenzyl)-pyrazole-3- carboxamide) in the modulation of certain AC isoforms in transiently transfected COS-7 cells. We found that CB2 in COS cells has a constitutive activity, and thus leading to inhibition of AC-V activity even in the absence of agonist. In addition, this constitutive modulation of AC is reversed by SR144528. It is now well established that several G protein-coupled receptors can signal without agonist stimulation(constitutive receptors). Inverse agonists have been shown to inhibit the activity of such constitutive G protein-coupled receptor signaling. Agonist activation of the G$\_$i/o/-coupled peripheral cannabinoid receptor CB2 normally inhibits adenylyl cyclase type V and stimulates adenylyl cyclase type II. Using transfected COS cells, we show here that application of SR144528, an inverse agonist of CB2, leads to a reverse action (stimulation of adenylyl cyclase V and inhibition of adenylyl cyclase II). This inverse agonism of SR144528 is dependent on the temperature, as well as on the concentration of the cDNA of CB2 transfected. Pertussis toxin blocked the regulation of adenylyl cyclase activity by SR 144528.

• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.442-450
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• 2024

The type-1 cannabinoid receptor (CB₁R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB₁R ligands. In this study, CB₁R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB₁R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB₁R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB₁R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB₁R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB₁R, which can be used to control psychiatric disorders and drug abuse.

• 대한생식의학회:학술대회논문집
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• 2006.11a
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• pp.146-147
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• 2006

• Toxicological Research
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• v.35 no.1
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• pp.37-44
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• 2019

A major predictor of the efficacy of natural or synthetic cannabinoids is their binding affinity to the cannabinoid type I receptor ($CB_1$) in the central nervous system, as the main psychological effects of cannabinoids are achieved via binding to this receptor. Conventionally, receptor binding assays have been performed using isotopes, which are inconvenient owing to the effects of radioactivity. In the present study, the binding affinities of five cannabinoids for purified $CB_1$ were measured using a surface plasmon resonance (SPR) technique as a putative non-isotopic receptor binding assay. Results were compared with those of a radio-isotope-labeled receptor binding assay. The representative natural cannabinoid ${\Delta}^9$-tetrahydrocannabinol and four synthetic cannabinoids, JWH-015, JWH-210, RCS-4, and JWH-250, were assessed using both the SPR biosensor assay and the conventional isotopic receptor binding assay. The binding affinities of the test substances to $CB_1$ were determined to be (from highest to lowest) $9.52{\times}10^{-3}M$ (JWH-210), $6.54{\times}10^{-12}M$ (JWH-250), $1.56{\times}10^{-11}M$ (${\Delta}^9$-tetrahydrocannabinol), $2.75{\times}10^{-11}M$ (RCS-4), and $6.80{\times}10^{-11}M$ (JWH-015) using the non-isotopic method. Using the conventional isotopic receptor binding assay, the same order of affinities was observed. In conclusion, our results support the use of kinetic analysis via SPR in place of the isotopic receptor binding assay. To replace the receptor binding affinity assay with SPR techniques in routine assays, further studies for method validation will be needed in the future.

• The Journal of Pediatrics of Korean Medicine
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• v.34 no.4
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• pp.11-21
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• 2020

Objectives This study aimed to investigate the efficacy of Ephedra sinica (E. sinica), Panax ginseng (P. ginseng), and Alisma orientale (A. orientale) Extract (MIT) on insulin resistance induced by Non-alcoholic fatty liver disease (NAFLD). Methods C57BL /6 male mice (8-week-old, 20 g) were divided into four groups: control group (Ctrl), high-fat diet group (HFDF), high fat diet with metformin administration group (METT), and high fat diet with MIT administration group (MITT). Each 10 mice were allocated to each group (a total of 40 mice). All mice were allowed to eat fat-rich diet freely throughout the experiment. To examine the effect of MIT, we observed Cannabinoid receptor type 1 (CB1), Cannabinoid receptor type 2 (CB2), G protein-coupled receptor 55 (GPR55), and Transforming growth factor-β (TGF-β). Results In the MITT group, positive reactions of the CB1, CB2, and GPR55 were significantly was significantly suppressed compared to the HFDF group. The positive reactions of the CD36 and TGF-β in the liver tissue were significantly suppressed in MITT. Conclusions MIT has the effect of improving NAFLD induced insulin resistance through the regulation of the lipid metabolism.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.218-224
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• 2015

Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor ${\gamma}$($PPAR{\gamma}$). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the $CB_1$ receptor, TRPV1 and $PPAR{\gamma}$. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on $PPAR{\gamma}$ transactivation. AEA can directly activate $PPAR{\gamma}$. The effect of AEA on $PPAR{\gamma}$ in hBM-MSCs may prevail over that on the $CB_1$ receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the $PPAR{\gamma}$ activity in the $PPAR{\gamma}$ transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a $CB_1$ antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the $CB_1$ receptor. This result suggests that the constantly active $CB_1$ receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective $CB_1$ agonists that are unable to affect cellular $PPAR{\gamma}$ activity inhibit adipogenesis in hBM-MSCs.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.45-45
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• 2021

This study aimed to explore research on bibliometric features of cannabis by applying scientometric analysis method, and to approach experimental research evaluation based on it. A total of 30,352 articles on cannabis published since 2001 from SCOPUS were analyzed using KnowledgeMatrix Plus and VOSviewer software. Results showed differences in research activities in countries where cannabis is legalized (Canada, the United States, the Netherlands) and Asian countries where its use is illegal. Related to medical cannabis, there has been a noticeable increase in the number of studies on pain, epilepsy, seizures and brain diseases such as multiple sclerosis. In the field of basic research, the number of pharmacological studies of cannabis on the cannabinoid type 1 receptor signaling pathway and inflammation and obesity has increased significantly. Subsequent experimental studies have compared the anti-inflammatory effects of four parts of Korean cannabis such as root, stem, leaf, and bark. Consistent with the predicted results of the scientometric analysis, all parts of C. sativa showed inhibitory effects on COX-2, NO/iNOS and TNF-α expression in LPS-stimulated RAW264.7 cells. These attempts provide an experimental research approach based on scientometric assessment.