• Natural Product Sciences
• /
• 제18권2호
• /
• pp.67-75
• /
• 2012

Zizyphi Spinosi Semen (ZSS) have been widely used for the treatment of insomnia in Asia. This experiment was performed to investigate whether methanol extract of ZSS (MEZSS) has hypnotic effects through the ${\gamma}$-amino butyric acid (GABA)ergic systems. MEZSS inhibited the locomotor activity. MEZSS enhanced pentobarbital-induced sleep behaviors. However, MEZSS itself did not induce sleep at higher dose, similar to muscimol. On the other hand, both pentobarbital and MEZSS increased the non rapid eye move (NREM) sleep, especially reducing the -wave electroencephalogram (EEG) activity in REM sleep. MEZSS showed similar effects with muscimol on potentiating chloride influx induced by pentobarbital. MEZSS significantly increased GABAA receptors ${\gamma}$-subunit expression and slightly decreased ${\beta}$-subunit expression in hypothalamus and thalamus, showing that subunit-expression was similar to diazepam. In addition, MEZSS enhanced the expression of glutamic acid decarboxylase (GAD). In conclusion, it is suggested that MEZSS might augment pentobarbital-induced sleep behaviors through the modification of GABAergic systems.

• Archives of Pharmacal Research
• /
• 제27권1호
• /
• pp.94-98
• /
• 2004

Effects of dopaminergic drugs on the degranulation of mast cells (RBL-2H3 cells) and the nitric oxide production from macrophage cells (RAW 264.7) were studied. Among the dopaminergic agonists and antagonists tested, bromocriptine, 7-OH-DPAT, haloperidol, and clozapine showed potent inhibitions of mast cell degranualtion ($IC_{50} value, 5 \mu$ M). However, these dopaminergic agents did not affect the tyrosine phosphorylations of the signaling components of the high affinity IgE receptor ($Fc\varepsilonRI$), such as Syk, $PLC\gamma1$, and $PLC\gamma2$.; This suggested that these signaling components were not involved in the inhibition of the mast cell degranulation by these compounds. On the other hand, dopamine, bromocriptine, 7-OH-DAPT, and haloperidol markedly inhibited the nitric oxide production from RAW 264.7 cells ($IC_{50}$ values, 10-20$\mu$M). Bromocriptine, a dopamine agonist that is routinely used for the treatment of Parkinsons disease, inhibited the expression of the inducible nitric oxide synthase at an early stage of the LPS-induced protein expression in a dose-dependent manner. The results suggested that these dopaminergic agents, when used for the treatment of dopamine receptors-related diseases, such as Schizophrenia or Parkinsons disease, might have additional beneficial effects.

• Clinical and Experimental Pediatrics
• /
• 제46권7호
• /
• pp.702-709
• /
• 2003

목 적 : $IFN{\gamma}$는 다양한 암세포에서 $TNF{\alpha}$와 FAS/CD95 수용체 발현을 증가시키거나 caspase나 Bcl-2 가족의 활성화를 조절하여 $TNF{\alpha}$와 FAS/FASL 유도성 세포고사를 촉진한다. 신경모세포종에서 $IFN{\gamma}$와 $TNF{\alpha}$는 협동적으로 세포 분화를 유도하거나 성장 억제를 일으킨다. 또한 일부 신경모세포종에서 자연적인 FAS 수용체 발현에도 불구하고 그 리간드 자극에 의한 세포고사 유도에는 실패하였고 $IFN{\gamma}$ 투여로 이를 극복할 수 있음이 보고되었다. 본 연구에서는 $IFN{\gamma}$가 $TNF{\alpha}$나 길항적 FAS/CD95 항체 유도성 세포고사를 촉진할 수 있는지 여부를 다양한 항암제에 대한 내성을 가지고 있는 신경모세포종 세포주를 이용하여 알아보았다. 방 법 : CHLA-15, CHLA-90와 LA-N-2 신경모세포종 세포주를 IMDM 배지로 배양하였고 유전자 재조합 $IFN{\gamma}$, $TNF{\alpha}$, 길항적 FAS/CD95 항체(CH-11)를 투여하였다. 세포 생존율은 형광기질인 calcein-AM을 이용한 DIMSCAN을 통하여 측정하였고, 세포고사 정도는 Annexin V-PE와 7-ADD염색을 이용한 유식세포 분석기를 통하여 분석하였고 pancaspase and caspase-8 억제 실험을 통하여 확인하였다. TNF와 FAS/CD95 수용체 표현은 각각에 대한 단클론 항체와 PE가 결합된 이차 항체를 이용하여 유식세포 분석기로 알아보았다. 결 과 : $IFN{\gamma}$ 또는 $TNF{\alpha}$ 단독 투여로는 모든 세포주에서 의의있는 세포 독성을 유도하지 못 했으나 $IFN{\gamma}$와 $TNF{\alpha}$을 병행 투여시에는 CHLA-15과 CHLA-90 세포주에서 의의있는 세포 생존율 감소와 공통 capase경로를 통한 세포고사를 협동적으로 촉진하였다. 또한 길항적 FAS/CD95 항체 단독 투여 시에는 모든 세포주에서 세포 생존율의 변화가 없었으나 $IFN{\gamma}$ 전 처치 후 투여 시에는 CHLA-90 세포주에서 현저한 세포 생존율 변화 및 세포고사를 유도하였다. $INF{\gamma}$ 치료 후 TNFRI와 FASR의 발현이 모든 세포주에서 현저히 증가하였는데 이는 일부 감수성이 있는 신경모세포종에서 $INF{\gamma}$에 의한 $TNF{\alpha}$와 FAS/CD95수용체 유도성 세포고사 촉진의 한 기전이 될 것으로 사료된다. 결 론: 일부 신경모세포종에서 $IFN{\gamma}$가 $TNF{\alpha}$와 길항적 FAS/CD95 항체 유도성 세포고사를 감작화 시켰으며 이는 수용체 발현의 증가와 동반되었다.

• Tuberculosis and Respiratory Diseases
• /
• 제58권1호
• /
• pp.11-17
• /
• 2005

연구배경 : 결핵의 발병에 유전적인 소인이 존재하며 숙주 면역 반응에 $IFN-{\gamma}$가 중요한 역할을 한다고 알려져 있다. 파종성 NTM 또는 BCG 감염증 환자에서 $IFN-{\gamma}$ 수용체 유전자 돌연변이가 밝혀져 있는데, 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍 유무는 잘 알려져 있지 않았다. 방 법 : 2개 이상의 장기를 침범한 파종성 결핵 환자 6명을 대상으로 염기순서분석을 통해 $IFN-{\gamma}$ 수용체 1과 $IFN-{\gamma}$ 수용체 2의 부분결핍을 초래하는 유전자 이상이 있는지를 살펴보았다. 결 과 : $IFN-{\gamma}R1$의 부분결핍을 초래하는 I87T와 818delT 818del4, 818insA 그리고 $IFN-{\gamma}R2$의 부분결핍을 초래하는 R114C 돌연변이 등 기존에 보고된 유전자 이상은 발견되지 않았다. 결 론 : 본 연구의 대상인 6명의 파종성 결핵 환자에서 $IFN-{\gamma}$ 수용체의 부분결핍을 초래하는 유전자 이상은 발견되지 않았다.

• International Journal of Oral Biology
• /
• 제37권1호
• /
• pp.1-7
• /
• 2012

Opioid receptors have been pharmacologically classified as ${\mu}$, ${\delta}$, ${\kappa}$ and ${\varepsilon}$. We have recently reported that the antinociceptive effect of morphine (a ${\mu}$-opioid receptor agonist), but not that of ${\beta}$-endorphin (a novel ${\mu}/{\varepsilon}$-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of ${\mu}-$, ${\delta}-$, ${\kappa}-$ and ${\varepsilon}$-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a $^{60}Co$ gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water ($52^{\circ}C$) tail-immersion test. Morphine and $D-Ala^2$, $N-Me-Phe^4$, Gly-olenkephalin (DAMGO), [$D-Pen^2-D-Pen^5$] enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide (U50,488H), and ${\beta}$-endorphin were tested as agonists for ${\mu}$, ${\delta}$, ${\kappa}$, and ${\varepsilon}$-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of ${\beta}$-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on ${\mu}-$ and ${\varepsilon}$-opioid receptor agonists, we assessed pretreatment effects of ${\beta}$-funaltrexamine (${\beta}$-FNA, a ${\mu}$-opioid receptor antagonist) or ${\beta}$-$endorphin_{1-27}$ (${\beta}$-$EP_{1-27}$, an ${\varepsilon}$-opioid receptor antagonist), and found that pretreatment with ${\beta}$-FNA significantly attenuated the antinociceptive effects of morphine and ${\beta}$-endorphin by WBI. ${\beta}$-$EP_{1-27}$ significantly reversed the attenuation of morphine by WBI and significantly attenuated the increased effects of ${\beta}$-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for ${\mu}-$ and ${\varepsilon}$-opioid receptors.

• The Korean Journal of Physiology and Pharmacology
• /
• 제18권6호
• /
• pp.509-516
• /
• 2014

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive $Ca^{2+}$ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of $Ca^{2+}$ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular $Ca^{2+}$ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (${\gamma}$)-irradiation. In irradiated RKO cells, $Ca^{2+}$ influx via activation of NCX reverse mode was enhanced and a decline of $[Ca^{2+}]_i$ via forward mode was accelerated. The amount of $Ca^{2+}$ released from the ER in RKO cells by the activation of $IP_3$ receptor was also enhanced by irradiation. An increase in $[Ca^{2+}]_i$ via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that ${\gamma}$-irradiation elicits enhancement of cellular $Ca^{2+}$ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

• Clinical and Experimental Pediatrics
• /
• 제56권4호
• /
• pp.151-158
• /
• 2013

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-${\alpha}$, PPAR-${\gamma}$, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-${\gamma}$ agonist. Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-${\alpha}$, transforming growth factor (TGF)-${\beta}$, PPAR-${\alpha}$ and PPAR-${\gamma}$ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid. Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPAR${\alpha}$ and PPAR-${\gamma}$ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-${\alpha}$, and TGF-${\beta}$ mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-${\beta}$ expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid. Conclusion: PPAR-${\alpha}$ and PPAR-${\gamma}$ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.

• 대한불안의학회지
• /
• 제2권2호
• /
• pp.79-85
• /
• 2006

Anxiety and anxiety disorders are related to many neurotransmitters, such as norepinephrine, serotonine, dopamine, glutamate, and Gamma-aminobutyric acid (GABA). GABA, the main inhibitory neurotransmitter of the CNS, is known to counterbalance the action of the excitatory neurotransmitters and control anxiety. GABA acts on 3 GABA receptor subtypes, $GABA_A$, $GABA_B$, and $GABA_C$. $GABA_A$ and $GABA_c$ receptors are oligomeric transmembrane glycoproteins composed of 5 subunits that are arranged around a central chloride channel. $GABA_B$ receptor comprises two 7-transmembraneis-spanning proteins that are coupled to either calcium or potassium channel via G proteins. This article highlights neurobiological interactions between anxiety and GABA system.

• Asian-Australasian Journal of Animal Sciences
• /
• 제22권2호
• /
• pp.296-304
• /
• 2009

The nutritional significance of essential amino acids, as well as non-essential amino acids, is well documented in poultry production with regards to growth performance and protein accretion. However, the function of amino acids in the stress response is still unclear. L-Pipecolic acid, a L-lysine metabolite in the brain, induced a hypnotic and sedative effect acting via the ${\gamma}$- aminobutyric acid receptors. L-Arginine also induced a sedative effect via its metabolism to L-ornithine. In addition, three-carbon nonessential amino acids like L-alanine, L-serine and L-cysteine also induced sedative effects. These facts suggest that the requirement for amino acids in both essential and non-essential types may require reconsideration to add the concept of stress amelioration in the future.

• 한국작물학회지
• /
• 제57권2호
• /
• pp.144-150
• /
• 2012

${\gamma}$-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plant and animal kingdom. GABA is found in tissues of the central nervous system (CNS) in animals. GABA functions as a the major inhibitory neurotransmitter in the CNS by acting through the GABA receptors. Clinical studies have revealed the relationship between an increased intake of GABA or analogues with several health benefits, including lowering of blood pressure in mildly hypertensive animals and humans. Furthermore, GABA would also has an inhibitory effect on cancer cell proliferation, stimulates cancer cell apoptosis and plays a role in alcohol-associated diseases and schizophrenia. In plants, interest in the GABA emerged mainly from experimental observations that GABA is largely and rapidly produced in large amounts in response to biotic and abiotic stresses. In this study, we speculated the properties and metabolism of GABA in plant and functions in relation to the responses to environmental stresses.