• 제목/요약/키워드: 5HT5A receptor

검색결과 157건 처리시간 0.027초

기분장애 및 기분관련장애에서 세로토닌 수용체 유전자 프로모터 다형성 (Serotonin(2A) Receptor Gene Promoter Polymorphism in Mood Disorder and Mood-Related Disorders)

  • 지익성
    • 생물정신의학
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    • 제9권1호
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    • pp.3-7
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    • 2002
  • Genes involved in the serotonin system are good candidates for the pathogenesis of mood disorder and mood-related disorders, such as eating disorder, obsessive-compulsive disorder, alcoholism, and suicide. Serotonin type 2A(5-HT2A) receptor gene promoter polymorphism(-1438A/G) has been reported. In this article, authors reviewed the literatures regarding association studies between -1438A/G and mood disorder and mood-related disorders. There are controversial results with limited data to date. Further researches on the -1438A/G in psychiatric disorders are required.

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Antipsychotics for patients with pain

  • Shin, Sang Wook;Lee, Jin Seong;Abdi, Salahadin;Lee, Su Jung;Kim, Kyung Hoon
    • The Korean Journal of Pain
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    • 제32권1호
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    • pp.3-11
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    • 2019
  • Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (${\alpha}$), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak $D_2$ receptor bindings with strong binding to the $5-HT_{2A}$ receptor, while typical antipsychotics block long-lasting, tight $D_2$ receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

전침자극(電鍼刺戟)의 Collagen 유발 관절염(關節炎) 동물(動物)모델에 대한 진통효과(鎭痛效果) 및 기전(機轉)에 관한 연구(硏究) -Serotonergic Mechanism을 중심으로- (The Analgesic Effect and Its Mechanism of Electroacupuncture in the Type II Collagen-induced Arthritis Rats : Mediation by Serotonergic Receptors)

  • 류성룡;백용현;박동석
    • Journal of Acupuncture Research
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    • 제23권3호
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    • pp.77-90
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    • 2006
  • Objectives : To evaluate the analgesic effect of electroacupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes $(5-HT_{1A},\;5-HT_{1B},\;5-HT_4)$ in the antinociceptive effect of electroacupuncture in the thermal hyperalgesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type II collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 14 days later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization. EA stimulation (2Hz, 0.07mA, 0.3ms) was delivered into Choksamni for 20 minutes. We measured the analgesic effect of EA with TFL afer intraperitoneal injection of normal saline, WAYl00635, SB216641 and GR125487. Results : TFLs were gradually decreased in CIA as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. EA stimulation on ST36 inhibited chronic inflammatory pain induced by CIA. The analgesic effect of EA was inhibited by pretreatment of $5-HT_{1A}$. antagonist (WAYl00635), $5-HT_{1B}$ antagonist (SB216641) and $5-HT_4$ antagonist (GR125487). Conclusion : Electroacupuncture has the analgesic effect on chronic inflammatory pain and its mechanism was mediated by $5-HT_{1A}$, $5-HT_{1B}$ and $5-HT_4$.

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Effect of serotonin on the cell viability of the bovine mammary alveolar cell-T (MAC-T) cell line

  • Xusheng, Dong;Chen, Liu;Jialin, Miao;Xueyan, Lin;Yun, Wang;Zhonghua, Wang;Qiuling, Hou
    • Journal of Animal Science and Technology
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    • 제64권5호
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    • pp.922-936
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    • 2022
  • 5-Hydroxytryptamine (5-HT), a monoamine, as a local regulator in the mammary gland is a chemical signal produced by the mammary epithelium cell. In cows, studies have shown that 5-HT is associated with epithelial cell apoptosis during the degenerative phase of the mammary gland. However, studies in other tissues have shown that 5-HT can effectively promote cell viability. Whether 5-HT could have an effect on mammary cell viability in dairy cows is still unknown. The purpose of this study was to determine: (1) effect of 5-HT on the viability of bovine mammary epithelial cells and its related signaling pathways, (2) interaction between prolactin (PRL) and 5-HT on the cell viability. The bovine mammary alveolar cell-T (MAC-T) were cultured with different concentrations of 5-HT for 12, 24, 48 or 72 hours, and then were assayed using cell counting kit-8, polymerase chain reaction (PCR) and immunobloting. The results suggested that 20 μM 5-HT treatment for 12 or 24 h promote cell viability, which was mainly induced by the activation of 5-HT receptor (5-HTR) 1B and 4, because the increase caused by 5-HT vanished when 5-HTR 1B and 4 was blocked by SB224289 and SB204070. And protein expression of mammalian target of rapamycin (mTOR), eukaryotic translation elongation factor 2 (eEF2), janus kinase 2 (JAK2) and signal transducer and activator of transcription 5 (STAT5) were decreased after blocking 5-HT 1B and 4 receptors. When MAC-T cells were treated with 5-HT and PRL simultaneously for 24 h, both the cell viability and the level of mTOR protein were significantly higher than that cultured with 5-HT or PRL alone. In conclusion, our study suggested that 5-HT promotes the viability of MAC-T cells by 5-HTR 1B and/or 4. Furthermore, there is a reciprocal relationship between PRL and 5-HT.

Amperozide Decreases Cocaine-Induced Increase in Behavior and Immediate Early Gene Expression in the Dorsal Striatum

  • Choe, Eun-Sang;Kim, Jong-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • 제4권5호
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    • pp.361-367
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    • 2000
  • Cocaine functions as indirect dopamine and serotonin (5-hydroxytryptamine, 5HT) agonists and induces genomic and behavioral alterations in the striatum. Previously we demonstrated that ritanserin, a 5HT2/1C receptor antagonist, is not responsible for cocaine-induced behavioral alterations and zif268 mRNA gene expression in the striatum (see the previous paper in this issue). In this study, it was hypothesized that dopamine and 5HT2/1C receptors are required for cocaine-induced behavioral alterations and c-fos and zif268 mRNA expression. This hypothesis was addressed by infusing amperozide which antagonizes both 5HT2/1C and dopamine receptors and was analyzed using the quantitative in situ hybridization histochemistry in vivo. Systemic injection of amperozide (5 mg/kg, s.c.) significantly blocked increase in behavior, c-fos and zif268 mRNA expression induced by 15 mg/kg cocaine, i.p., in the dorsal striatum. These data suggest that dopamine and 5HT2/1C receptors are necessary for cocaine-induced behavioral alterations and immediate early gene expression in the dorsal striatum.

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Binding Mode Prediction of 5-Hydroxytryptamine 2C Receptor Ligands by Homology Modeling and Molecular Docking Analysis

  • Ahmed, Asif;Nagarajan, Shanthi;Doddareddy, Munikumar Reddy;Cho, Yong-Seo;Pae, Ae-Nim
    • Bulletin of the Korean Chemical Society
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    • 제32권6호
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    • pp.2008-2014
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    • 2011
  • Serotonin or 5-hydroxytryptamine subtype 2C ($5-HT_{2C}$) receptor belongs to class A amine subfamily of G-protein-coupled receptor (GPCR) super family and its ligands has therapeutic promise as anti-depressant and -obesity agents. So far, bovine rhodopsin from class A opsin subfamily was the mostly used X-ray crystal template to model this receptor. Here, we explained homology model using beta 2 adrenergic receptor (${\beta}$2AR), the model was energetically minimized and validated by flexible ligand docking with known agonists and antagonists. In the active site Asp134, Ser138 of transmembrane 3 (TM3), Arg195 of extracellular loop 2 (ECL2) and Tyr358 of TM7 were found as important residues to interact with agonists. In addition to these, V208 of ECL2 and N351 of TM7 was found to interact with antagonists. Several conserved residues including Trp324, Phe327 and Phe328 were also found to contribute hydrophobic interaction. The predicted ligand binding mode is in good agreement with published mutagenesis and homology model data. This new template derived homology model can be useful for further virtual screening based lead identification.

Developmental Disability Animal Model Based on Neonatal Lipopolysaccharide with Altered 5-HT Function

  • Kim, Jae-Goo;Kim, Min-Soo;Lee, Se-Oul;Kim, Gun-Tae;Lee, Jong-Doo;Kim, Dong-Goo
    • The Korean Journal of Physiology and Pharmacology
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    • 제11권3호
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    • pp.113-119
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    • 2007
  • Developmental disability shows life-long behavioral abnormality with no significant physical malformation. This study was undertaken to develop an animal model for developmental disability by using two-factor approach. Lipopolysaccharide (LPS), a bacterial toxin, and NAN-190, a $5-HT_{1A}$ receptor antagonist, were administered to Sprague-Dawley rats on postnatal day (PND) 5 to induce inflammation and an altered 5-HT system, respectively. Long-term alteration of behavior occurred in the drug-treated groups. The LPS-treated group showed impaired motor coordination in the Rota-rod test. The LPS- treated or both LPS and NAN-190-treated groups showed impaired fore-paw muscle power in the wire maneuver test. These groups also showed decreased white matter volume and increased serotonergic fibers. The LPS and NAN-190-treated group also exhibited neurologic deficit in the placing reaction test and impaired equilibrium function in the tilt table test. The results showed that a variety of altered behaviors can be generated by two factor model, and suggested that combination of important etiologic factors and possible underlying defects is a promising strategy of establishing an animal model for developmental disabilities.

Effect of Snake Venom Toxin on Inhibition of Colorectal Cancer HT29 Cells Growth via Death Receptors Mediated Apoptosis

  • Shim, Yoon Seop;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • 제31권2호
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    • pp.87-98
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    • 2014
  • Objectives : We investigated whether snake venom toxin(SVT) from Vipera lebetina turanica sensitizes HT29 human epithelial colorectal cancer cells to tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL) induced apoptosis in cancer cells. Methods : Cell viability assay was used to assess the inhibitory effect of TRAIL on cell growth of HT29 human colorectal cancer cells. And 6-diamidino-2-phenylindole(DAPI), terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay(TUNEL) staining assay were used to evaluate cell-apoptosis. Western blot analysis were conducted to observe apoptosis related proteins and death receptor. To assess whether the synergized inhibitory effect of SVT and TRAIL on reactive oxygen species(ROS) generation was reversed by strong anti-oxidative agent. Results : SVT with TRAIL inhibited HT29 cell growth different from TRAIL alone. Consistent with cell growth inhibition, the expression of TRAIL receptors; Expression of death receptor(DR)4 and DR5 was significantly increased and intrinsic pro-apoptotic cleaved caspase-3, -9 was subsequently increased together with increase of Bax/Bcl-2 ratio and extrinsic pro-apototic caspase-8 was also activated. In addition, the expression of anti-apoptotic survival proteins, a marker of TRAIL resistance(eg, cFLIP, survivin, X-linked inhibitor of apoptosis protein(XIAP) and Bcl-2) was suppressed by the combination treatment of SVT and TRAIL. Pretreatment with the ROS scavenger N-acetylcysteine abolished the SVT and TRAIL-induced upregulation of DR4 and DR5 expression and expression of the intrinsic pro-apoptotic caspase-3 and-9. Conclusion : The collective results suggest that SVT facilitates TRAIL-induced apoptosis in $HT_{29}$ human epithelial colorectal cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 and consecutive induction of bilateral apoptosis via regulating apoptosis related proteins.

인간의 대장암 HT-29 세포주에서 라이코펜이 Insulin-like Growth Factor-I Receptor Signaling Pathway에 미치는 영향 (Effect of Lycopene on the Insulin-like Growth Factor-I Receptor Signaling Pathway in Human Colon Cancer HT-29 Cells)

  • 이현숙;정재인;강영희;;윤정한
    • 한국식품영양과학회지
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    • 제32권3호
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    • pp.437-443
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    • 2003
  • 선행연구에서 라이코펜이 HT-29세포의 증식을 억제하는 것을 관찰하였기 때문에 본 연구는 그 기전을 연구하기 위하여 수행되 었다. 라이코펜이 HT-29 세포의 사멸을 유도하는지 조사하기 위해서 여러 농도의 라이코펜이 포함된 배지에서 세포를 4일 동안 배양하였다. 라이코펜 농도의 증가에 따라 사멸되는 세포에서 나타나는 특징의 하나인 DNA fragmentation이 증가하는 것을 관찰하였다. Western blot을 수행하여 얻은 결과에 의하면 라이코펜이 IGF-IR, IRS-1, PI3K, Akt와 같은 IGF-IR pathway에 속하는 단백질의 수준을 감소시켰다. IGF-IR의 인산화를 유도하기 위해서 라이코펜이 포함된 배지에서 세포를 배양하고 IGF-I을 첨가하여 0, 5, 10, 60분간 배양한 다음 IGF-IR antibody를 이용하여 immunoprecipitation을 수행하였다. 라이코펜은 IGF-I에 의한 IGF-IR, IRS-1의 인산화와 IGF-IR와 PI3K의 결합을 감소하고 인산화된 Akt를 감소시켰다. 이와 같은 IGF-IR signaling의 억제는 이 대장암세포에 존재하는 IGF-II의 autocrine loop을 억제하는 원인이 될 수 있어, 라이코펜의 암세포증식을 억제하는 기전 중의 하나가 될 수 있다. 라이코펜은 토마토와 그 가공품에 많이 존재하는 물질로 자연적인 식사를 통해 많이 섭취할 수 있는 물질이다. 라이코펜의 항암 기전을 밝혀냄으로써 미래 암예방과 치료를 위한 중요한 기능성 영양소를 생산할 수 있는 기초를 마련해줄 수 있을 것으로 기대된다.

뇌실내 TFMPP가 가토신장기능에 미치는 효과 (Effects of Intracerebroventricular TFMPP on Rabbit Renal Function)

  • 임영채;최종범;김경근;국영종
    • 대한약리학회지
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    • 제28권2호
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    • pp.137-146
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    • 1992
  • 신장기능조절에 있어서 중추 tryptamine계가 관련되어 있으며, $5-HT_1$수용체는 이뇨적인 역할을 하고 있는 반면에 $5-HT_2$$5-HT_3$수용체는 항이뇨적인 영향을 미치고 있음이 밝혀진 바 있다. 또한 $5-HT_1$수용체도 단일하지 않고 여러 subtype가 존재함이 알려져 있다. $5-HT_{1A}$수용체의 역할에 관해서는 신기능에 이뇨적인 영향을 미치고 있음이 시사된 바 있다. 본 연구에서는 중추 tryptamine성 신기능 조절에 있어서 $5-HT_{1B}$수용체의 역할을 구명하고자 하였다. 선택적 $5-HT_{1B}$ agonist인 TFMPP $8{\sim}750\;{\mu}g/kg$을 가토 측뇌실내로 투여하면 투여량에 비례하여 이뇨 및 Na과 K 배설의 증가를 초래하였으며, $250\;{\mu}g/kg$ 투여시에는 Na의 배설 분획이 5.44%까지 증가하였다. Na배설 촉진작용은 신혈류역학의 증가 보다도 훨씬 지속하여, 세뇨관에서의 Na재흡수 감소작용이 체액성 기전임을 시사하였다. TFMPP $250\;{\mu}g/kg$ icv투여시에 natriuresis와 함께 혈장내 atrial natriuretic peptide 농도가 약 6배 증가되었다. TFMPP $250\;{\mu}g/kg$을 정맥내로 투여하였을때는 뇌실내 투여시와는 상이하게 신기능에 별다른 유의한 변동을 초래하지 않았다. 이와같은 TFMPP의 diuresis 및 natriuresis는 각각 $5-HT_2$$5-HT_3$ 수용체의 선택적 antagonist인 ketanserin과 MDL 72222의 전처치에 의하여 차단되지 않았으며, methysergide에 의해서도 억제되지 않았다. 또한 $5-HT_{1A}$ antagonist로 알려진 NAN-190도 TFMPP의 작용을 차단하지 못하였으며 S(-)-propranolol도 영향을 미치지 않았다. 본 연구의 결과 중추 $5-HT_{1B}$수용체는 신장기능에 이뇨 및 Na배설 촉진적인 영향을 미치고 있고 이작용에 atrial natriuretic peptide가 관여함을 알 수 있었다.

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