• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.192-192
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• 1996

Endothelin has $ET_{A}$ type and $ET_{B}$ type receptors, and it has been thought that ET-1 proves vasoconstriction effect via $ET_{A}$ receptor and vasodilation via $ET_{B}$ receptor. Recently, it has been reported that $ET_{B}$ receptor is also related to the vaso-constriction. Bosentan is a $ET_{A+B}$ receptor antagonist, and proves it's effect on trauma and ischemia. We already announced that the level of Endothelin-1 increase in the brain and spinal cord of EAE-induced lewis rat and showed the origin of ET-1 is activated macrophages. Intracisternal injection of Bosentan, $ET_{A+B}$ receptor antagonist, (300nmol/body) was done for observing the role of endothelin-1 on the pathogenesis of EAE. Bosentan ameliorated the severity of clinical score of EAE and decreased the histologically observed inflammatory region. The blocking effect on the progression of EAE model suggests that Bosentan is a physiological antagonist in terms of development of the sign of multiple sclerosis.

• Biomolecules & Therapeutics
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• v.13 no.3
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• pp.138-142
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• 2005

Adenosine and GABA are known to be major inhitory neurotransmitters in the central nervous system and its receptors mediate various neurophamacological effects including cardiovascular modulatory effects. Inhibitory cardiovascular effects induced by intrathecal (i.t.) administration of adenosine $A_1$ receptor agonist and its modulation by cyclic AMP was suggested by our previous report. In this experiment, we examined the modulation of cardiovascular effects of adenosine $A_1$ receptor and adenosine $A_2$ receptor by $GABA_B$ receptors antagonist in the spinal cord. I.t. administration of 10 nmol of $N^6$-cyclohexyladenosine (CHA, an adenosine $A_1$ receptor agonist), I.t. administration of 2 nmol of 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA, an adenosine $A_2$ receptor agonist), pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CHA and pretreatment with 5-aminovaleric acid (a $GABA_B$ receptor antagonist, 50 nmol, i.t.) prior to administration of CPCA were performed in anesthetized, artificially ventilated Sprague-Dawley rats. I.t. administration of 50 nmol of 5-aminovaleric acid significantly attenuated the inhibitory cardiovascular effects of CHA but did not attenuated the inhibitory cardiovascular effects of CPCA. It is suggested that cardiovascular responses of adenosine $A_1$ receptor is modulated by $GABA_B$ receptor and adenosine $A_2$ receptor is not modulated by $GABA_B$ receptor in the spinal cord.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.277-283
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• 2013

In this study, we investigated the effects of a selective urotensin II (UII) receptor antagonist, SB-657510, on the inflmmatory response induced by UII in human umbilical vein endothelial cells (EA.hy926) and human monocytes (U937). UII induced inflammatory activation of endothelial cells through expression of proinflammatory cytokines (IL-$1{\beta}$ and IL-6), adhesion molecules (VCAM-1), and tissue factor (TF), which facilitates the adhesion of monocytes to EA.hy926 cells. Treatment with SB-657510 significantly inhibited UII-induced expression of IL-$1{\beta}$, IL-6, and VCAM-1 in EA.hy926 cells. Further, SB-657510 dramatically blocked the UII-induced increase in adhesion between U937 and EA.hy926 cells. In addition, SB-657510 remarkably reduced UII-induced expression of TF in EA.hy926 cells. Taken together, our results demonstrate that the UII antagonist SB-657510 decreases the progression of inflammation induced by UII in endothelial cells.

• YAKHAK HOEJI
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• v.35 no.5
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• pp.416-426
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• 1991

The effects of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin) on $\alpha_1$-adrenoceptor-mediated vasoconstrictions were studied in the endothelium-denuded rat aorta. In these experiments, the mobilization of intracelluier calcium and translocation of extracellular calcium were also studied. To exclude the modulation of endothelium releasing EDRF and EDCF, the endothelium was removed in all rat aortas. Contraction induced by phenylephrine (a full $\alpha_1$-adrenoceptor agonist) was separated into a fast phasic component of the response due to the release of intracellular calcium and a slow tonic one due to the influx of extracellular calcium. Pretreatments with increasing doses of reversible $\alpha_1$-adrenoceptor antagonist prazosin, as well as irreversible $\alpha_1$-adrenoceptor antagonist dibenamine, inhibited the phasic component of phenylephrine-induced contraction more effectively than the tonic one. Pretreatment of dibenamine (0.2 $\mu{M}$) or prazosin (10 nM) to the rat aorta abolished phasic response but remained tonic one about 41% and 51%, respectively. These results suggest that as the efficiency of phenylephrine was progressively reduced by pretreatments with increasing doses of an irreversible or a reversible $\alpha_1$-adrenoceptor antagonist (dibenamine or prazosin), the contraction induced by phenylephrine became progressively more dependent on the influx of extracellular calcium.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.311-317
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• 1996

Background: Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. Previous studies have shown this allodynia was reversed by intrathecal alpha-2 agonists and NMDA antagonists, but not by morphine. In formalin test, either the pretreatment of NMDA antagonist or morphine prevents the hyperalgesia. The present studies, using rats rendered allodynic by ligation of the left L5 and L6 nerves, aimed to investigate the effects of pretreatment of MK-801 and morphine on the development of tactile allodynia. Methods and Material: Male Sprague-Dawley rats (100~150g) were anesthetized with halothane, the left L5 and L6 spinal nerves were ligated tightly by 6-0 black silk. For sham operation muscle dissection was performed but the spinal nerve was not ligated. For pretreatment of drugs, MK-801 (NMDA antagonist; 0.3 mg/kg). CNQX (non-NMDA) antagonist; 0.3 mg/kg), morphine (1 mg/kg) or saline (placebo) was administered subcutaneously 30 minutes before operation. A second dose was administered subcutaneously 24 hours after operation and further doses were given daily for 2 days further. The volume of injection was 5 ml/kg. To assess the mechanical allodynia, paw withdrawal thresholds of ipsilateral limb were determined using 8 von Frey hairs. Results: Within 2 days saline, CNQX or morphine injected rats developed tactile allodynia (paw withdrawal threshold was about 2g), and persisted for over 2 weeks. Pretreatment of MK-801 delayed the development of tactile allodynia for 3 days comparing to that of saline injected rat. Conclusion: NMDA receptor in the central nerve system plays an important role in the development of tactile allodynia induced by peripheral nerve injury. But the mechanism may be different from hyperalgesia developed in formalin test.

• The Journal of Advanced Prosthodontics
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• v.14 no.2
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• pp.122-132
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• 2022

PURPOSE. This in-vitro analysis aimed to compare the intaglio trueness, the antagonist's wear volume loss, and fracture load of various single-unit zirconia prostheses fabricated by different manufacturing techniques. MATERIALS AND METHODS. Zirconia crowns were prepared into four different groups (n = 14 per group) according to the manufacturing techniques and generations of the materials. The intaglio surface trueness (root-mean-square estimates, RMS) of the crown was measured at the marginal, axial, occlusal, and inner surface areas. Half of the specimens were artificially aged in the chewing simulator with 120,000 cycles, and the antagonist's volume loss after aging was calculated. The fracture load for each crown group was measured before and after hydrothermal aging. The intaglio trueness was evaluated with Welch's ANOVA and the antagonist's volume loss was assessed by the Kruskal-Wallis tests. The effects of manufacturing and aging on the fracture resistance of the tested zirconia crowns were determined by two-way ANOVA. RESULTS. The trueness analysis of the crown intaglio surfaces showed surface deviation (RMS) within 50 ㎛, regardless of the manufacturing methods (P = .053). After simulated mastication, no significant differences in the volume loss of the antagonists were observed among the zirconia groups (P = .946). The manufacturing methods and simulated chewing had statistically significant effects on the fracture resistance (P < .001). CONCLUSION. The intaglio surface trueness, fracture resistance, and antagonist's wear volume of the additively manufactured 3Y-TZP crown were clinically acceptable, as compared with those of the 4Y- or 5Y-PSZ crowns produced by subtractive milling.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.285-289
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• 2011

Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Shilajit has been reported to be an injury and muscular pain reliever but there have been few functional studies of the effect of Shilajit on the SG neurons of the Vc. Therefore, whole cell and gramicidin-perfotrated patch clamp studies were performed to examine the action mechanism of Shilajit on the SG neurons of Vc from mouse brainstem slices. In the whole cell patch clamp mode, Shilajit induced short-lived and repeatable inward currents under the condition of a high chloride pipette solution on all the SG neurons tested. The Shilajit-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated $Na^+$ channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, and AP5, an NMDA receptor antagonist. The Shilajit-induced responses were partially suppressed by picrotoxin, a $GABA_A$ receptor antagonist, and totally blocked in the presence of strychnine, a glycine receptor antagonist, however not affected by mecamylamine hydrochloride (MCH), a nicotinic acetylcholine receptor antagonist. Under the potassium gluconate pipette solution at holding potential 0 mV, Shilajit induced repeatable outward current. These results show that Shilajit has inhibitory effects on the SG neurons of Vc through chloride ion channels by activation of the glycine receptor and $GABA_A$ receptor, indicating that Shilajit contains sedating ingredients for the central nervous system. These results also suggest that Shilajit may be a potential target for modulating orofacial pain processing.

• Molecules and Cells
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• v.25 no.1
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• pp.91-98
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• 2008

The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

• Biomolecules & Therapeutics
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• v.27 no.6
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• pp.584-590
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• 2019

Luteolin, a widespread flavonoid, has been known to have neuroprotective activity against various neurologic diseases such as epilepsy, and Alzheimer's disease. However, little information is available regarding the hypnotic effect of luteolin. In this study, we evaluated the hypnotic effect of luteolin and its underlying mechanism. In pentobarbital-induced sleeping mice model, luteolin (1, and 3 mg/kg, p.o.) decreased sleep latency and increased the total sleep time. Through electroencephalogram (EEG) and electromyogram (EMG) recording, we demonstrated that luteolin increased non-rapid eye movement (NREM) sleep time and decreased wake time. To evaluate the underlying mechanism, we examined the effects of various pharmacological antagonists on the hypnotic effect of luteolin. The hypnotic effect of 3 mg/kg of luteolin was not affected by flumazenil, a GABAA receptorbenzodiazepine (GABAAR-BDZ) binding site antagonist, and bicuculine, a GABAAR-GABA binding site antagonist. On the other hand, the hypnotic effect of 3 mg/kg of luteolin was almost completely blocked by caffeine, an antagonist for both adenosine A1 and A2A receptor (A1R and A2AR), 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), an A1R antagonist, and SCH-58261, an A2AR antagonist. From the binding affinity assay, we have found that luteolin significantly binds to not only A1R but also A2AR with $IC_{50}$ of 1.19, $0.84{\mu}g/kg$, respectively. However, luteolin did not bind to either BDZ-receptor or GABAAR. From these results, it has been suggested that luteolin has hypnotic efficacy through A1R and A2AR binding.

• Clinical and Experimental Reproductive Medicine
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• v.43 no.4
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• pp.233-239
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• 2016

Objective: Uterine contraction induced by the embryo transfer (ET) process has an adverse effect on embryo implantation. The aim of this study was to determine the effect of oxytocin antagonist supplementation on the day of ET on in vitro fertilization outcomes via a meta-analysis. Methods: We performed a meta-analysis of randomized controlled trials (RCTs). Four online databases (Embase, Medline, PubMed, and Cochrane Library) were searched through May 2015 for RCTs that investigated oxytocin antagonist supplementation on the day of ET. Studies were selected according to predefined inclusion criteria and meta-analyzed using RevMan 5.3. Only RCTs were included in this study. The main outcome measures were the clinical pregnancy rate, the implantation rate, and the miscarriage rate. Results: A total of 123 studies were reviewed and assessed for eligibility. Three RCTs, which included 1,020 patients, met the selection criteria. The implantation rate was significantly better in patients who underwent oxytocin antagonist infusion (19.8%) than in the control group (11.3%) (n = 681; odds ratio [OR], 1.92; 95% confidence interval [CI], 1.25-2.96). No significant difference was found between the two groups in the clinical pregnancy rate (n = 1,020; OR, 1.57; 95% CI, 0.92-2.67) or the miscarriage rate (n = 456; OR, 0.76; 95% CI, 0.44-1.33). Conclusion: The results of this meta-analysis of the currently available literature suggest that the administration of an oxytocin antagonist on the day of ET improves the implantation rate but not the clinical pregnancy rate or miscarriage rate. Additional, large-scale, prospective, randomized studies are necessary to confirm these findings.