• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
• /
• pp.292-292
• /
• 1994

Catecholamines acting through ${\beta}$-adrenergic receptors regulate a wide range of metabolic activities in mammalian tissue. Of the various receptors coupled to adenylate cyclase, the ${\beta}$-adrenergic receptors are the most extensively characterized and have been purified from both nonmammal ian and mammal inn sources. However, most studies of the molecular properties of ${\beta}$-adrenergic receptors have been confined to peripheral tissues. Less progress has been achieved in characterizing the brain ${\beta}$-adrenergic receptor The goal of the present study was, therefore, to purify and characterize the neurotransmitter receptor proteins. To achieve this goal, the following stepwise experiments were performed. At first, the membrane-bound ${\beta}$-adrenergic receptors were. solubi1ized from brain tissue. Secondly, conditions for affinity chromatography were determined to purify the solubilized receptors effectively. Finally, the large-scale purification was performed and the characteristics of the purified ${\beta}$-adrenergic receptor were examined.

• 신재생에너지
• /
• 제20권1호
• /
• pp.126-134
• /
• 2024

Biogas, composed mainly of methane (CH₄) and carbon dioxide (CO₂), is a renewable gas that can serve as an alternative energy source. In this study, we developed a new microwave reformer and analyzed its reforming characteristics. We observed that higher temperatures of the microwave receptor led to increased reforming efficiency. By supplying appropriate amounts of methane and steam, we could prevent carbon generated from the thermal decomposition reaction of carbon dioxide from depositing on the catalytic active layer, thus avoiding the inhibition of catalytic activity. Hydrogen generation was enhanced when maintaining the biogas ratio and steam supply at adequate levels. Increasing the SiC ratio in the receptor improved the uniformity of temperature distribution and growth rate, resulting in higher conversion rates of the reforming process.

• 한국발생생물학회:학술대회논문집
• /
• 한국발생생물학회 2001년도 후기 제12차 학술대회 논문집
• /
• pp.23-25
• /
• 2001

1. Leptin itself was not expressed in mouse uterine tissues. 2. Leptin receptors were not expressed in nonpregnant and little expressed in 3.5 day of pregnant uterine tissues. However, there was a signal in 4.5 and 5.5 day of tissues. 3. The expression level of leptin receptor variants in the implantation sites at around the time of initial embryo attachment (day 4.5 of pregnancy) and during the actual implantation period (day 5.5 of pregnancy) was much lower than that in the interimplantation 4. Finding of the differential expression of leptin receptors in implantation sites compared to interimplantation sites suggests that leptin - leptin receptor system may be one of the delicate regulators in the molecular mechanism of the implantation process.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1996년도 춘계학술대회
• /
• pp.19-29
• /
• 1996

The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

• Environmental Analysis Health and Toxicology
• /
• 제20권1호
• /
• pp.39-45
• /
• 2005

Renin-angiotensin system (RAS)은 혈압 조절에 중요한 역할을 수행하는 생리적 조절계로써, 이 system 을 구성하는 유전자들의 이상은 본태성 고혈압의 발병과 유의하게 관련된 것으로 알려졌다. RAS의 주요한 구성 성분인 angiotensin II는 2종류의 수용체인 angiotensin II type I receptor(AT₁R)와 angiotensin II type I receptor(AT₂R)에 의해 그 효과가 매개되기 때문에, 이 수용체를 암호하는 유전자는 본태성 고혈압의 유력한 후보 유전자라고 볼 수 있다. 현재가지의 연구에 의하면, AT₁R 유전자에 존재하는 유전적 변이와 본태성 고혈압과의 관련성에 관해서는 많은 보고들이 있었지만, AT₂R 유전자에 존재하는 유전적 변이 가 본태성 고혈압에 유의한 효과를 나타내는 지에 관해서는 이렇다할 연구 성과가 별로 없는 실정이다. 이에 본 연구에서는 한국인 집단을 대상으로 하여, AT₂R 유전자에 존재하는 C3123A 다형성이 한국인 집단에서 본태성 고혈압과 유의한 관련성이 있는 지를 분석하였다. 이 유전자는 인간의 X 염색체에 존재하기 때문에, 여성인 경우에는 CC, CA및 AA로 이루어진 3유전자형이 존재하지만, 남성인 경우에는 C와 A로 이루어진 2종류의 대립 유전자로 구성되어 있기 때문에, 본 연구에서는 남성과 여성을 개별적으로 나누어서 분석하였다. 연구 결과, AT₂R 유전자에 존재하는 C3123A 다형성은 남녀 모두에서 본태성 고혈압과 유의한 관련성을 나타내지 않았다(P>0.05). 그렇지만, 이 다형성에 대한 대립 유전자 빈도를 서양인 집단과 비교했을 경우에는, 한국인을 대상으로 한 본 연구에서 A 대립 유전자 빈도가 0.33인 반면에 서양인 집단은 그 빈도가 0.43～0.48로 한국인 집단보다 높은 값을 나타내었다. 따라서, AT₂R 유전자에 존재하는 C3123A 다형성과 본태성 고혈압과의 관련성에 대해서는 한국인과 유전적 배경이 다른 서양인 집단을 대상으로 한 추시가 필요할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
• /
• 제55권5호
• /
• pp.478-487
• /
• 2003

연구배경 : Angiotensin II가 폐포상피세포의 세포사멸을 유도하고 폐섬유모세포에서 TGF-${\beta}$등의 발현을 증가시켜 폐섬유화증을 촉진시킬 수 있다고 알려져 있어 angiotensin II receptor의 차단이 폐섬유화증을 감소시키는 효과가 있을 것으로 예상하고 특발성 폐섬유화증 환자에게 angiotensin II receptor antagonist(AGIIRA)를 투여하여 치료효과를 알아보고자 하였다. 방 법 : 저자들은 가천의대 길병원에서 특발성 폐섬유화증으로 진단된 13명의 환자를 대상으로 하였다. 이들 중 8명 의 환자에게는 angiotensin II type 1 receptor antaginist인 losartan(cozaar$^{(R)}$) 을 투여하였고 나머지 5명의 환자에게는 losartan을 투여 하지 않았으며, 치료 직전과 치료 l년 후에 모든 환자에게 폐기능 검사와 호흡곤란 지수의 정도의 변화를 측정하여 그 결과를 비교하였다. 결 과 : AGIIRA 복용 군에서는 폐기능이 전체적으로 약간의 호전을 보였으며, 미 복용 군에서는 DLco%가 5%로 증가하였으나 TLC가 14%로 감소하는 등 전반적으로 페기능이 감소하는 소견을 보였다. 폐기능 변화가 두 군 모두 통계적으로 유의성이 없었고 두 군간의 변화율의 변화에서도 통계적 유의성은 없었다. 호흡곤란 지수는 AGIIRA 복용한 군에서만 통계적으로 유의하게 더 호전을 보였다. 결 론 : 특발성 폐섬유화증의 치료에 AGIIRA가 일부 환자들에게 임상적 안정화에 도움을 줄 수 있을 것으로 사료된다. 차후 더 많은 환자를 대상으로 오랜 기간의 연구와 함께 폐섬유화에 있어서 anglotensin II와 그 receptor에 대한 기전과 역할에 대하여 더 많은 연구가 필요할 것으로 생각된다.

• 대한의생명과학회지
• /
• 제23권4호
• /
• pp.327-332
• /
• 2017

A2B adenosine receptor (A2BAR) is known to be a regulator of bone homeostasis, but the regulatory mechanism of A2BAR on the osteoclast proliferation are poorly explored. Recently, we have shown that stimulation with BAY 60-6583, a specific agonist of A2BAR, significantly reduced macrophage-colony stimulating factor (M-CSF)-induced osteoclast proliferation by inducing cell cycle arrest at G1 phase and increasing the apoptosis of osteoclasts. The objective of this study was to investigate the regulatory mechanisms of cell cycle and apoptosis by A2BAR stimulation. The expression of A2BAR and M-CSF receptor, c-Fms, was not changed by A2BAR stimulation whereas M-CSF effectively induced c-Fms expression during osteoclast proliferation. Interestingly, A2BAR stimulation remarkably increased the expression of $p27^{Kip-1}$, a cell cycle inhibitor, but the expression of Cyclin D1 and cdk4 was not affected. In addition, while BAY 60-6583 treatment reduced the expression of Bcl2, an anti-apoptotic oncogene, it failed to regulate the expression of Bax, a pro-apoptotic marker. Taken together, these results imply that the increase of $p27^{Kip-1}$ inducing cell cycle arrest at G1 phase and the decrease of Bcl2 inducing anti-apoptotic response by A2BAR stimulation contribute to the down-regulation of osteoclast proliferation.

• 약학회지
• /
• 제45권2호
• /
• pp.205-213
• /
• 2001

The dopaminergic receptors were consisted of two distinct subtypes, $D_1$and $D_2$, each having different function. The present study was attempted to investigate the effects of R(-)-2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA), a dopamine $D_2$receptor agonist, on renal function in dog. TNPA (5.0~15.0 $\mu$g/kg), when given into the vein, produced a dose-dependently antidiuresis along with the decrease in osmolar clearance ( $C_{osm}$) and urinary excretion of sodium and potassium ( $E_{Na}$ , and $E_{K}$). It also increased reabsorption rates of sodium and potassium in renal tubules ( $R_{Na}$ , $R_{K}$) without any changes in glomerular filtration rate (GFR), renal plasma flow (RPF) and free water clearance ( $C_{H2o}$). TNPA (0.5~1.5 $\mu$g/kg/min) infused into a renal artery decreased urine flow both in the experimental and the control kidneys. TNPA (1.5~5.0 $\mu$g/kg) administered via the carotid artery also greatly exhibited antidiuresis even at intravenously ineffective doses. Changes of renal function by TNPA given into both the renal artery and the carotid artery were almost the same aspect to those induced by intravenous TNPA. These results obtained from the present study suggest that TNPA produces antidiuresis by increasing the reabsorption rates of electrolytes in renal tubules, mainly distal tubule, through changing of central function.unction.

• Biomolecules & Therapeutics
• /
• 제18권3호
• /
• pp.316-320
• /
• 2010

Pruritus is one of major symptoms in atopic dermatis. The pathophysiological mechanism of pruritus is unclear. The search for pruritogen is important in elucidating the pathophysiological mechanism of pruritus in atopic dermatitis. Glucosylsphingosine (Gsp) is upregulated in the strateum corneum of atopic dermatitis patients. We investigated to determine whether Gsp induces itch-scratch responses (ISRs) in mice. Intradermal administration of Gsp induces ISRs. Gsp dose-dependently induced scratching response at 50-500 nmol/site range. Pretreatment with naltrexone, an opioid $\mu$ receptor antagonist, and capsaicin, a TrpV1 receptor agonist, inhibited Gsp-induced ISRs. Additionally, Gsp-induced ISRs were also suppressed by cyproheptadine, an antagonist of serotonin receptor. These findings suggest that Gsp-induced scratching might be at least partly mediated by capsaicin-sensitive primary afferents, and the opioids receptor systems might be involved in transmission of itch signaling in the central nervous system. Furthermore, our findings suggest that Gsp-induced ISRs may be attributable to the serotonin-mediated pathways and Gsp is not any more one of byproducts of abnormal skin barrier but can lead to induce pruritus, one of typical symptoms of atopic dermatitis.

• International Journal of Oral Biology
• /
• 제33권1호
• /
• pp.1-5
• /
• 2008

Adenosine 5'-triphosphate (ATP) is an important extracellular signaling molecule which is involved in a variety of physiological responses in many different tissues and cell types, by acting at P2 receptors, either ionotropic (P2X) or G protein-coupled metabotropic receptors (P2Y). P2X receptors have seven isoforms designated as $P2X_{1^-}P2X_7$. In this study, we investigated the electrophysiological and pharmacological properties of rat $P2X_{1^-}P2X_4$ currents by using whole-cell patch clamp technique in a heterologous expression system. When ATP-induced currents were analyzed in human embryonic kidney (HEK293) cells following transient transfection of rat $P2X_{1^-}P2X_4$, the currents showed different pharmacological and electrophysiological properties. ATP evoked inward currents with fast activation and fast desensitization in $P2X_{^1-}$ or $P2X_{3^-}$ expressing HEK293 cells, but in $P2X_{2^-}$ or $P2X_{4^-}$ expressing HEK293 cells, ATP evoked inward currents with slow activation and slow desensitization. While PPADS and suramin inhibited $P2X_2$ or $P2X_3$ receptor-mediated currents, they had little effects on $P2X_4$ receptor-mediated currents. Ivermectin potentiated and prolonged $P2X_4$ receptor-mediated currents, but did not affect $P2X_2$ or $P2X_3$ receptor-mediated currents. We suggest that distinct pharmacological and electrophysiological properties among P2X receptor subtypes would be a useful tool to determine expression patterns of P2X receptors in the nervous system including trigeminal sensory neurons and microglia.