• Journal of Life Science
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• v.31 no.7
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• pp.662-670
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• 2021

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal (GI) muscles that generate the rhythmic oscillation in membrane potentials known as slow waves. In the present study, we investigated the effects of mirtazapine, a noradrenergic and serotonergic antidepressant, on pacemaking potential in cultured ICCs from the murine small intestine. The whole-cell patch-clamp configuration was used to record pacemaker potential in cultured ICCs. Mirtazapine induced pacemaker potential depolarizations in a concentration-dependent manner in the current clamp mode. Y25130 (a 5-HT3 receptor antagonist), RS39604 (a 5-HT4 receptor antagonist), and SB269970 (a 5-HT7 receptor antagonist) had no effects on mirtazapine-induced pacemaker potential depolarizations. Also, methoctramine, a muscarinic M₂ receptor antagonist, had no effect on mirtazapine-induced pacemaker potential depolarizations, whereas 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a muscarinic M₃ receptor antagonist, inhibited the depolarizations. When guanosine 5'-[β-thio] diphosphate (GDP-β-S; 1 mM) was in the pipette solution, mirtazapine-induced pacemaker potential depolarization was blocked. When an external Ca²⁺ free solution or thapsigargin, a Ca²⁺-ATPase inhibitor of the endoplasmic reticulum, was applied, the generation of pacemaker potentials disappeared, and under these conditions, mirtazapine induced pacemaker potential depolarizations. In addition, protein kinase C (PKC) inhibitor, calphostin C, and chelerythrine inhibited mirtazapine-induced pacemaker potential depolarizations. These results suggest that mirtazapine regulates pacemaker potentials through muscarinic M₃ receptor activation via a G protein-dependent and an external or internal Ca²⁺-independent PKC pathway in the ICCs. Therefore, mirtazapine can control GI motility through ICCs.

• Journal of Life Science
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• v.29 no.9
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• pp.1010-1015
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• 2019

The interstitial cells of Cajal (ICCs) are the pacemaker cells in the gastrointestinal (GI) tract. In the present study, the effects of olanzapine, an atypical antipsychotic agent, on pacemaker potentials in cultured ICCs from the small intestine of the mouse were investigated. The whole-cell patch-clamp configuration was used to record pacemaker potentials from cultured ICCs. Olanzapine produced pacemaker depolarizations in a concentration-dependent manner in current clamp mode. Methoctramine, a muscarinic $M_2$ receptor antagonist, did not inhibit olanzapine-induced pacemaker depolarizations, whereas 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) muscarinic $M_3$ receptor antagonist did inhibit it. When guanosine 5'-[${\beta}$-thio] diphosphate (GDP-${\beta}$-S; 1 mM) was in the pipette solution, olanzapine-induced pacemaker depolarization was blocked. Also, low $Na^+$ solution externally eliminated the generation of pacemaker potentials and inhibited the olanzapine-induced pacemaker depolarizations. Additionally, the nonselective cation channel blocker, flufenamic acid, inhibited the olanzapine-induced pacemaker depolarizations. Pretreatment with U-73122, an active phospholipase C (PLC) inhibitor, also eliminated the generation of pacemaker potentials and suppressed the olanzapine-induced pacemaker depolarizations. These results suggested that olanzapine modulates the pacemaker potentials through muscarinic $M_3$ receptor activation by G protein-dependent external $Na^+$ and PLC pathway in the ICCs. Therefore, olanzapine could affect intestinal motility through ICCs.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.271-279
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• 2019

The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current ($I_{Gly}$). Firstly, we examined with a $5-HT_1$ receptor agonist (8-OH-DPAT, $5-HT_{1/7}$ agonist, co-applied with SB-269970, $5-HT_7$ antagonist) and antagonist (WAY-100635), but $5-HT_1$ receptor agonist did not increase $I_{Gly}$ and in the presence of $5-HT_1$ antagonist, the potentiation of 5-HT on $I_{Gly}$ still happened. However, an agonist (${\alpha}$-methyl-5-HT) and antagonist (ketanserin) of the $5-HT_2$ receptor mimicked and inhibited the enhancing effect of 5-HT on $I_{Gly}$ in the SG neurons, respectively. We also verified the role of the $5-HT_7$ receptor by using a $5-HT_7$ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on $I_{Gly}$. Our study demonstrated that 5-HT facilitated $I_{Gly}$ in the SG neurons of the Vc through the $5-HT_2$ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

• Journal of Ginseng Research
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• v.45 no.1
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• pp.66-74
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• 2021

Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

• Journal of Korean Society of Forest Science
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• v.87 no.3
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• pp.358-365
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• 1998

To offer the basic information for sustainable production of forest resources and conservation of the global environment, change in potential natural vegetation (PNV) associated with climate change due to doubling atmospheric carbon dioxide ($2{\times}CO_2$) was estimated with the global natural vegetation mapping system based an K${\ddot{o}}$ppen scheme. The system interpolates climate data spherically to each grid cell, determines the vegetation types onto the grid cell, and produces potential vegetation map and area on the globe and continents. The climate data consist of the current, ($1{\times}CO_2$) climate prior to AD 1958 observed at some 2,000 stations and the doubling ($2{\times}CO_2$) climate estimated from Meteorological Research Institute of Japan. The vegetation zone under the $2{\times}CO_2$ climate scenario expanded mainly toward the poles due to the rise in temperature. The changed PNV area on the globe amounts to 1/3 (4.91 billion (G) ha) of the total land area (15.04 Gha). Kappa statistic for judging agreement between the patterns of vegetation distribution under $1{\times}CO_2$ climate and $2{\times}CO_2$ climates shows good agreement (0.63) for the globe as a whole. The most stable areas are desert and ice. The potential forest area (PFA) was estimated at 6.82 Gha of the land area in $2{\times}CO_2$ climate scenario. In terms of continental changes in PFA, North America and Asis are increased under the $2{\times}CO_2$ climate. However, the potential forest arms of the other continents are decreased by the climate. Europe has no change in the PFA. Especially, the expansion of desert area in Oceania would be accelerated by the $2{\times}CO_2$ climate.

• The Sea:JOURNAL OF THE KOREAN SOCIETY OF OCEANOGRAPHY
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• v.7 no.2
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• pp.68-77
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• 2002

We investigated the outbreak, maintenance, and decline of the red tide dominated by C. polykrikoides in the coastal waters off Southern Korea from August to October, 2000, by combining field data and NOAA satellite images. In general, the C. polykrikoides blooms, which have occured annually in Korean coastal waters from 1995 to 1999, initiate between late August and early September around Narodo Island and expand to the whole area of the southern coast. However, initiation and short-term change of the bloom of 2000 were quite different from the pattern observed previously. In mid-August, thermal fronts in sea surface temperature(SST) were formed: 1) between the Tsushima Warm Current Water (TWCW) and the Southern Korean Coastal Waters (SKCW), 2) between the jindo cold water mass and the southwestern coastal waters, and 3) between the upwelled cold waters in the southeast coast and the offshore warm waters. Free-living cells of C. polykrikoides were concentrated in these frontal regions. In late August, the thermal front TWCW-SKCW approached the mouth of Yeosuhae Bay where Seomjin River water and anthropogenic pollutants from the Industrial Complex of Gwangyang Bay are discharged. In the blooms of 2000 initiated in Yeosuhae Bay in late August, the dominant species, C. polykrikoides, co-occured with Alexandrum tamarense, Gymnodinium mikimotoi, Skeletonema coastatum, and Chaetoceros spp. Two typhoons, 'Prapiroon' and 'Saomai' during and the C. polykrikoides bloom probably affected the abundance of this species. After the former typhoon passed the Korean Peninsula, cell growth of C. polykrikoides was maximal, but after the latter typhoon, the C. polykrikoides bloom disappeared (20 September). On 5 October, the blooms dominated by C. polykrikoides broke out within the coastal waters of Jinhae Bay and Hansan-Keoje Bay. NOAA satellite images showed that the isothermal line of 22$^{\circ}C$ extended into Jinhae Bay. In this bloom, C. polykrikoides also occurred simultaneously with Akashiwo sanguinea(=Gym-nodinium sangunium), a common red tide-forming dinoflagellate species in fall and winter in these coastal bays.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.535-563
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• 1993

New techniques for regenerating the destructed periodontal tissue have been studied for many years. Current acceptable methods of promoting periodontal regeneration alre basis of removal of diseased soft tissue, root treatment, guided tissue regeneration, graft materials, biological mediators. Platelet-derived growth factor (PDGF) is one of polypeptide growth factor. PDGF have been reported as a biological mediator which regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the possibility of using the PDGF as a regeneration promoting agent for furcation involvement defect. Eight adult mongrel dogs were used in this experiment. The dogs were anesthetized with Pentobarbital Sodium (25-30 mg/kg of body weight, Tokyo chemical Co., Japan) and conventional periodontal prophylaxis were performed with ultrasonic scaler. With intrasulcular and crestal incision, mucoperiosteal flap was elevated. Following decortication with 1/2 high speed round bur, degree III furcation defect was made on mandibular second(P2) and fourth(P4) premolar. For the basic treatment of root surface, fully saturated citric acid was applied on the exposed root surface for 3 minutes. On the right P4 20ug of human recombinant PDGF-BB dissolved in acetic acid was applied with polypropylene autopipette. On the left P2 and right P2 PDGF-BB was applied after insertion of ${\beta}-Tricalcium$ phosphate(TCP) and collagen (Collatape) respectively. Left mandibular P4 was used as control. Systemic antibiotics (Penicillin-G benzathine and penicillin-G procaine, 1 ml per 10-25 1bs body weight) were administrated intramuscular for 2 weeks after surgery. Irrigation with 0.1% Chlorhexidine Gluconate around operated sites was performed during the whole experimental period except one day immediate after surgery. Soft diets were fed through the whole experiment period. After 2, 4, 8, 12 weeks, the animals were sacrificed by perfusion technique. Tissue block was excised including the tooth and prepared for light microscope with H-E staining. At 2 weeks after surgery, therer were rapid osteogenesis phenomenon on the defected area of the PDGF only treated group and early trabeculation pattern was made with new osteoid tissue produced by activated osteoblast. Bone formation was almost completed to the fornix of furcation by 8 weeks after surgery. New cementum fromation was observed from 2 weeks after surgery, and the thickness was increased until 8 weeks with typical Sharpey’s fibers reembedded into new bone and cementum. In both PDGF-BB with TCP group and PDGF-BB with Collagen group, regeneration process including new bone and new cementum formation and the group especially in the early weeks. It might be thought that the migration of actively proliferating cells was prohibited by the graft materials. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.