• Biomolecules & Therapeutics
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• 제24권5호
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• pp.517-522
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• 2016

${\beta}$-Arrestins are one of the protein families that interact with G protein-coupled receptors (GPCRs). The roles of ${\beta}$-arrestins are multifaceted, as they mediate different processes including receptor desensitization, endocytosis, and G protein-independent signaling. Thus, determining the GPCR regions involved in the interactions with ${\beta}$-arrestins would be a preliminary step in understanding the molecular mechanisms involved in the selective direction of each function. In the current study, we determined the roles of the N-terminus, intracellular loops, and C-terminal tail of a representative GPCR in the interaction with ${\beta}$-arrestin2. For this, we employed dopamine $D_2$ and $D_3$ receptors ($D_2R$ and $D_3R$, respectively), since they display distinct agonist-induced interactions with ${\beta}$-arrestins. Our results showed that the second and third intracellular loops of $D_2R$ are involved in the agonist-induced translocation of ${\beta}$-arrestins toward plasma membranes. In contrast, the N- and C-termini of $D_2R$ exerted negative effects on the basal interaction with ${\beta}$-arrestins.

• Clinical and Experimental Reproductive Medicine
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• 제18권2호
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• pp.201-208
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• 1991

Recently the application of gonadotropin-releasing hormone (GnRH) agonist to superovulation in previous poor responders has resulted in the improved outcomes after in vitro fertilization (IVF) outcome. However, poor responders with poor estradiol $(E_2)$ rise or single dominant follicle are a particularly challenging group. Recent reports have also shown that patients with higher basal serum follicle stimulating hormone (FSH) level, result in poorer ovarian response and lower pregnancy rate. Analysis of the differences of superovulation outcomes according to the different protocols of GnRH agonist, long (L, n = 18) and short (S, n = 16) protocols, in patients with high basal FSH levels (>20mIU/ml) were undertaken at Seoul National University Hospital from June to October 1990. The administration of GnRH agonist was begun on day 21 of the cycle in long protocol, and on day 2 in short protocol. Ages of patients and husbands, basal FSH and luteinizing hormone (LH) levels and FSH/LH ratio did not differ significantly. Types and causes of infertility were evenly distributed. Whereas the duration of stimulation and the amounts of gonadotropins administered were significantly reduced in short protocol, the numbers of oocytes retrieved and cleaved, the cleavage rate and the number of embryos transferred were higher in long protocol without statistical signifieance. The pregnancy rate per ET was 16.7% (2/12) in short protocol, and 17.6% (3/17) in long protocol. These data suggest that both protocols result in the similar superovulation outcomes in patients with higher basal serum FSH levels.

• International Journal of Oral Biology
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• 제30권3호
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• pp.91-98
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• 2005

Gamma-aminobutyric acid (GABA) is known as an inhibitory neurotransmitter in the neurons of the central nervous system. However, its detailed action mechanisms in the rostral gustatory zone of the nucleus tractus solitarius (rNTS) have not been established. The present study was aimed to investigate the distribution, role and action mechanisms of GABA in rNTS. Membrane potentials were recorded by whole cell recordings in isolated brain slices of the rat medulla. Superfusion of GABA resulted in a concentration-dependent reduction in input resistance in the neurons in rNTS. The change in input resistance ws accompanied by response to a depolarizing pulse were diminished by GABA. Superfusion of the slices with either $GABA_A$ agonist, muscimol, $GABA_B$ agonist, baclofen or $GABA_C$ agonist, TACA, decreased input resistance and reduced the nerve activity in association with membrane hyperpolarization. It is suggested that inhibitory signals playa role in sensory processing by the rNTS, in that GABA actions occur through activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptor. These results suggest that GABA has an inhibitory effect on the rNTS through an activation of $GABA_A,\;GABA_B\;and\;GABA_C$ receptors and that the GABAergic inhibition probably plays an important role in sensory processing by the rNTS.

• 대한통합의학회지
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• 제3권4호
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• pp.29-35
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• 2015

Purpose: The purpose of this study was to effect of application methods of stretching exercise on angular variation and muscle activation changes in the hallux valgus. Method : This study was performed on twenty subjects. Twenty subjects were divided into two groups; Agonist Contraction(AC)(n=10), Hold-relax with Agonist Contraction(HR-AC)(n=10). Both of the group performed the exercise 5 times a week for 6 weeks. The data was analyzed by the paired t-test for comparing before and after changes of factors in each group and the independent t-test for comparing the between groups. Result : In the within group comparisons, HR-AC group abductor hallucis muscle activity showed significant difference between before and after the intervention(p<0.01). And all the two groups, there were significant decreased in hallux valgus angle(p<0.01). In the comparison of the two groups, there were significant difference among the two groups in abductor hallucis muscle activity(p<0.01). Conclusion : The findings of this study, we found that the HR-AC technique were more effective than AC technique in increase in abductor hallucis muscle activity.

• Restorative Dentistry and Endodontics
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• 제31권3호
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• pp.203-214
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• 2006

치수는 상아질로 둘러싸인 간엽조직으로 다양한 세포와 기저 물질들로 구성되어 있으며 혈관과 신경조직이 분포되어 있다. 치수의 염증은 조직의 분해를 야기하며 이는 Matrix Metalloproteinase에 의해 세포 외 기질의 분해가 촉진되어 병적인 과정을 거치게 된다. 이에 Lipopolysaccharide에 의한 MMP와 inflammatory cytokine의 유도와 peroxisome proliferator-activated receptors (PPAR)에 의한 염증매개 물질의 조절에 대해 알아보고자 하였다. 사람의 치수세포를 다양한 LPS농도에 노출시킨 후 24시간째 MMP-2, MMP-9의 변화를 보고 LPS에 의해 자극된 치수세포에서 ICAM-1, VCAM-1, $IL-1{\beta},\;TNF-{\alpha}$의 분비가 증가됨을 알 수 있었다. 또한 Adenovirus $PPAR{\gamma}\;(Ad/PPAR{\gamma})$와 $PPAR{\gamma}$ agonist인 rosiglitazone를 LPS로 자극된 치수세포에 처리하였을 때 48시간째 MMPs와 Adhesion molecules, cytokines의 감소를 확인하였다. 이로써 사람의 치수세포에서 $PPAR{\gamma}$가 가지는 항 염증효과에 대해 지속적 인 연구가 필요할 것으로 사료된다.

• 생명과학회지
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• 제10권4호
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• pp.374-379
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• 2000

This study was attempted to evaluate an agonistic activity to benzodiazepine receptor of several medicinal pants, which have been used as sedatives in oriental medicine. The activities of the methanol extracts of composite preparation of oriental drugs were compared with those of the simple drugs, furthermore, the active fraction was found out from the simple preparation. Inhibitory effects of composite preparations, Cyperus rotundus/Acorus gramineus, Thuja orientalis/Euphoria longan, Thuja orientalis/Albizzia julibrissin, on the binding of ${[^3H]}$Ro15-1788, a selective benszodiazepine receptor antagonist to benzodiazepine receptor of rat cortices, were observed to be lower than those of corresponding simple preparations. These unexpected results suggest that some components of the composite druge may rather act as an obstacle, not to show the sinergistic effect. The methanol extracts of Cyperus rotundus having the highest activity were fractionated using polar and nonpolar solvents to give ethylacetate and hexane fractions, respectively. The ethylacetate fraction containing relatively polar components exhibited much higher activity than the hexane fraction, which consiste of nonpolar agonist, binding to benzodiazepine receptor. However, in the presence of GABA, this fraction inhibited ${[^3H]}$flunitrazepan binding, and these positive GABA shift supported the strong possibility of agonistic activity to benzodiazepine receptro. As a result, it may be concluded that the substance or substances with neurochemical properties as a benzodiazepine receptor agonist may contribute to the sedative property of Cyperus rotundus.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.228-233
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• 2011

Objective: To investigate the effectiveness of GnRH antagonist multiple-dose protocol (MDP) with oral contraceptive pill (OCP) pretreatment in poor responders undergoing IVF/ICSI, compared with GnRH antagonist MDP without OCP pretreatment and GnRH agonist low-dose long protocol (LP). Methods: A total of 120 poor responders were randomized into three groups according to controlled ovarian stimulation (COS) options; GnRH antagonist MDP after OCP pretreatment (group 1), GnRH antagonist MDP without OCP pretreatment (group 2) or GnRH agonist luteal low-dose LP without OCP pretreatment (group 3). Patients allocated in group 1 were pretreated with OCP for 21days in the cycle preceding COS, and ovarian stimulation using recombinant human FSH (rhFSH) was started 5 days after discontinuation of OCP. Results: There were no differences in patients' characteristics among three groups. Total dose and days of rhFSH used for COS were significantly higher in group 3 than in group 1 or 2. The numbers of mature oocytes, fertilized oocytes and grade I, II embryos were significantly lower in group 2 than in group 1 or 3. There were no significant differences in the clinical pregnancy rate and implantation rate among three groups. Conclusion: GnRH antagonist MDP with OCP pretreatment is at least as effective as GnRH agonist low-dose LP in poor responders and can benefit the poor responders by reducing the amount and duration of FSH required for follicular maturation.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.251-258
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• 2002

Objective : The aim of this study was to evaluate the outcomes of the GnRH antagonist (Cetrotide) minimal stimulation protocol comparing with GnRH agonist combined long step down stimulation protocol in PCOS patients. Materials and Method: From Apr 2001 to May 2002, 22 patients (22 cycles) were performed in controlled ovarian hyperstimulation using by GnRH antagonist and GnRH agonist for PCOS patients. GnRH antagonist (Cetrotide) combined minimal stimulation protocol was administered in 10 patients (10 cycles, Study Group) and GnRH agonist long step down stimulation protocol was administered in 12 patients (12 cycles, Control Group). We compared the pregnancy rate/cycle, total FSH (A)/cycle, Retrieved oocyte/cycle, the incidence of ovarian hyperstimulation syndrome, multiple pregnancy rate between the two groups. Student-t test were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: Group of GnRH antagonist (Cetrorelix) minimal stimulation protocol produced fewer oocytes (6.4 versus 16.3 oocytes/cycle) using a lower dose of FSH (22.2 versus 36.1 Ample/cycle) and none developed OHSS and multiple pregnancy. Although the trends were in favour of the GnRH antagonist (Cetrorelix) protocol, the differences did not reach statistical significance. This was probably due to small sample size. Conclusion: The use of GnRH antagonist reduce the risk of ovarian hyperstimulation and multiple pregnancy. We suggest that GnRH antagonist might be alternative controlled ovarian hyperstimulation method, especially in PCOS patients who will be ovarian high response.

• 대한의생명과학회지
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• 제19권2호
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• pp.112-117
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• 2013

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of NF-${\kappa}B$, leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Triptolide (TP), a natural component of Tripterygium wilfordii Hook. F, has been used as folk remedies to treat many chronic diseases for many years. In the present report, we present biochemical evidence that TP inhibits the NF-${\kappa}B$ activation induced by polyriboinosinic polyribocytidylic acid (Poly[I:C], TLR3 agonist) and lipopolysaccharide (LPS, TLR4 agonist). TP also inhibits COX-2 expression induced by Poly[I:C] and LPS. These results suggest that TP can modulate the immune responses regulated by TLR3 and TLR4 signaling pathways.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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• pp.325-335
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• 1997

Evidence for the existance of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective $A_1$ adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of $A_2$ adenoisne receptor. N6-(L-2-phenylisoproryl)-adenosine (PIA) almost unselectively activates both $A_1\;and\;A_2$ adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic adminstration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.