• 제목/요약/키워드: $5-HT_2$ receptors

검색결과 77건 처리시간 0.026초

The Effect of Ethanol on 5-Hydrosytryptamine Receptor-Mediated Ion Current in Cultured NCB-20 Neuroblastoma Cells

  • Woo, Hyo-Geyng;Chung, In-Kyo;Cho, Goon-Jae;Chung, Yong-Za;Il Yun
    • Journal of Life Science
    • /
    • 제9권2호
    • /
    • pp.82-85
    • /
    • 1999
  • The effects of ethanol on 5-hydrosytryptamine(5-HT3) receptor-mediated ion current were evaluated in whole-cell patch-clamp recordings from NCB-20 neuroblastoma cells. The physiologic and pharmacologic properties of 5-HT-activated ion current in NCB-20 cells indicated that it was mediated by 5-HT3 receptors. Ethanol(25-100mM) potentiated 5-HT3 receptor-mediated current in a concentration-dependent manner.

메스암페타민 자발섭취가 흰쥐 뇌조직 중 세로토닌 수용체에 미치는 영향 (The Effects of Self-administration of Methamphetamine on Serotonin Receptors Level in Rat Brain)

  • 박기숙;홍진태;한진이;김혜진;김용규;이종권;안광수;이선희
    • Biomolecules & Therapeutics
    • /
    • 제9권2호
    • /
    • pp.88-95
    • /
    • 2001
  • (+)-Methamphetamine (METH) is a psychostimulant, which has been the most popular abused drug in Korea. The rewarding mechanism in METH abuse has been reported to be mediated by dopaminergic system. Recently, it has been reported that dopamine releaser (phentermine) plays a dominant role in the discriminative stimulus effects of METH, whereas 5-HT releaser (fenfluramine) can strongly modify METH self-administration. The present study is designed to assess the behavioral changes and the changes of the serotonin receptors in the brains of rats administered repeated of self-administered METH. The repeated administration of 1.0 mg/kg/day METH for 12 days increased locomotor activities, and there was no difference between i.v. and i.p. treatment. Rats had actively acquired METH self-administration for 3 weeks at 0.1 or 0.2 mg/kg/injection. Whereas, it was taken few days to acquire sucrose pellet self-administration. The binding of [$^3$H]-8-hydroxy-DPAT (5-H $T_{1A}$ receptors) and [$^3$H]-5-carboxytryptamine (5-H $T_{1B}$ receptors) to brain sections was examined. Both passive administration and self-administration of METH did not change significantly the serotonin receptors levels in hippocampus, striatum and nucleus accumbens. These results suggest that serotonin receptors may not change in the acquisition period of METH self-administration, and we are trying to investigate the serotonin receptors levels of brain in rats maintained of METH self-administration.n.n.

  • PDF

Antipsychotics for patients with pain

  • Shin, Sang Wook;Lee, Jin Seong;Abdi, Salahadin;Lee, Su Jung;Kim, Kyung Hoon
    • The Korean Journal of Pain
    • /
    • 제32권1호
    • /
    • pp.3-11
    • /
    • 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.

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

  • 임영채;최종범;김경근;국영종
    • 대한약리학회지
    • /
    • 제28권2호
    • /
    • pp.137-146
    • /
    • 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.

  • PDF

Structure-Activity Relationship and Evaluation of Phenethylamine and Tryptamine Derivatives for Affinity towards 5-Hydroxytryptamine Type 2A Receptor

  • Shujie, Wang;Anlin, Zhu;Suresh, Paudel;Choon-Gon, Jang;Yong Sup, Lee;Kyeong-Man, Kim
    • Biomolecules & Therapeutics
    • /
    • 제31권2호
    • /
    • pp.176-182
    • /
    • 2023
  • Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT2AR have been classified into three structural groups: phenethylamines, tryptamines, and ergolines. In this study, the structure-activity relationship (SAR) of phenethylamine and tryptamine derivatives for binding 5-HT2AR was determined. In addition, functional and regulatory evaluation of selected compounds was conducted for extracellular signal-regulated kinases (ERKs) and receptor endocytosis. SAR studies showed that phenethylamines possessed higher affinity to 5-HT2AR than tryptamines. In phenethylamines, two phenyl groups were attached to the carbon and nitrogen (R3 ) atoms of ethylamine, the backbone of phenethylamines. Alkyl or halogen groups on the phenyl ring attached to the β carbon exerted positive effects on the binding affinity when they were at para positions. Oxygen-containing groups attached to R3 exerted mixed influences depending on the position of their attachment. In tryptamine derivatives, tryptamine group was attached to the β carbon of ethylamine, and ally groups were attached to the nitrogen atom. Oxygen-containing substituents on large ring and alkyl substituents on the small ring of tryptamine groups exerted positive and negative influence on the affinity for 5-HT2AR, respectively. Ally groups attached to the nitrogen atom of ethylamine exerted negative influences. Functional and regulatory activities of the tested compounds correlated with their affinity for 5-HT2AR, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT2AR, which can be used to control psychiatric disorders and drug abuse.

Involvement of spinal muscarinic and serotonergic receptors in the anti-allodynic effect of electroacupuncture in rats with oxaliplatin-induced neuropathic pain

  • Lee, Ji Hwan;Go, Donghyun;Kim, Woojin;Lee, Giseog;Bae, Hyojeong;Quan, Fu Shi;Kim, Sun Kwang
    • The Korean Journal of Physiology and Pharmacology
    • /
    • 제20권4호
    • /
    • pp.407-414
    • /
    • 2016
  • This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

Pharmacophore Hypothesis for Atypical Antipsychotics

  • Sekhar, Kondapalli Venkata Gowri Chandra;Vyas, Devambhatla Ravi Kumar;Nagesh, Hunsur Nagendra;Rao, Vajja Sambasiva
    • Bulletin of the Korean Chemical Society
    • /
    • 제33권9호
    • /
    • pp.2930-2936
    • /
    • 2012
  • A three-dimensional pharmacophore hypothesis was developed for atypical antipsychotics in order to map common structural features of highly active compounds by using HipHop in CATALYST program. The pharmacophore hypotheses were generated using 12 compounds as training set and validated using 11 compounds as test set. The most predictive hypothesis (Hypo1) comprises five features viz. two hydrophobic regions, two hydrogen bond acceptor lipid and one aromatic ring. In the absence of information like crystallized structure of 5-$HT_{2A}$ receptor and binding mode of antipsychotics with 5-$HT_{2A}$ receptor, this hypothesis will serve as a potentially valuable tool in the design of novel atypical antipsychotics acting primarily at 5-$HT_{2A}$ and $D_2$ receptors.

Buspirone-induced Prolaction 분비와 $5-HT_{1A}$ 수용체: Pindolol 전처치 효과 (Buspirone-induced Prolactin Secretion in Man is Not $5-HT_{1A}$ Receptor Mediated: Effect of Pindolol Pretreatment)

  • 이홍식
    • 대한약리학회지
    • /
    • 제28권1호
    • /
    • pp.19-25
    • /
    • 1992
  • Nonbenzodiazepine계 항불안제인 buspirone을 이용하여 건강한 8명의 남자를 대상으로 prolactin과 cortisol분비를 측정하였다. Buspirone는 $Dopamine_2$ 수용체 antagonist 성질 뿐 아니라 $5-HT_{1A}$ partial agonist 효과가 있는 것으로 보고되고 있다. Buspirone 30mg 경구투여시 혈청 prolactin 농도는 유의한 증가를 보였으나 혈청 cortisol 농도의 변화는 차이가 없었다. beta adrenoreceptor antagonist이면서 $5-HT_{1A}$ 수용체 antagonist로 알려진 pindolol (30mg)을 경구 투여한 결과 기초 혈청 prolactin이나 cortisol 농도는 유의한 차이가 없었다. Pinodlol을 전처치한 경우 buspirone-induced prolaction 분비의 유의한 억제효과는 없었다. 이상의 성적은 buspirone-induced prolactin 분비증가는 아마도 $5-HT_{1A}$ 수용체 활성과 관련되지 않음을 시사하는 것으로 사료된다.

  • PDF

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
    • /
    • 제64권5호
    • /
    • pp.922-936
    • /
    • 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.

뇌간 신경세포 배양에서 세로토닌 분비에 대한 N-methyl-D-aspartic Acid(NMDA) 및 Non-NMDA 수용체 효현제들의 작용 (Effect of N-methyl-D-aspartic acid(NMDA)-and Non NMDA-Receptor Agonists on Serotonin Release from Cultured Neurons of Fetal Rat Brainstem)

  • 유순미;김율아;송동근;서홍원;김영희
    • 대한약리학회지
    • /
    • 제31권2호
    • /
    • pp.141-144
    • /
    • 1995
  • 뇌간의 세로트닌 신경계는 내재성 하행성 동통억제계(endogenous descending pain inhibitory system)에 있어서 중추적인 역할을 하고 있다. 뇌간의 세로토닌 신경세포에 대한 glutamate 수용체 중 N-methyl-D-aspartic acid-(NMDA-) 및 non-NMDA 수용체 효현제들의 작용을 알아보기 위하여, 쥐의 태자(태생 14일)로부터 뇌간을 분리하여 10일 동안 배양한 후 5-hydroxytryptamine(5-HT)의 분비에 대한 각 glutamate 수용체 효현제들이 영향을 연구하였다. Glutamate를 $10\;{\mu}M$에서 $1000\;{\mu}M$까지 농도를 변화하여 30분 동안 배지에 가한 후, 배지내에 분비되는 세로토닌을 측정한 결과, 농도 의존적으로 세로토닌의 분비가 증가되었다. Glutamate 수용체 중에서 NMDA 수용체 효현제인 NMDA를 $10\;{\mu}M$에서 $1000\;{\mu}M$까지 농도를 변화하여 30분 동안 배지에 가한 후, 배지내에 분비되는 세로토닌을 측정한 결과, 농도 의존적으로 세로토닌의 분비가 증가되었다. Non-NMDA 수용체 효현제인 kainate 및 AMPA를 $3\;{\mu}M$에서 $300\;{\mu}M$까지 농도를 변화하여 배지에 처리한 결과, 각 효현제에 의해 농도 의존적으로 세로토닌의 분비가 증가됨을 관찰하였다. 이상의 연구결과, 쥐의 태자(태생 14일)로부터 분리하여 10일동안 배양한 뇌간의 세로토닌 신경세포에 있어서 glutamate, NMDA, kainate 및 AMPA 모두 5-HT의 분비를 자극함으로써, NMDA- 및 non-NMDA 수용체 모두 5-HT의 분비에 관여하고 있음을 나타낸다.

  • PDF