• Genomics & Informatics
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• 제5권2호
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• pp.77-82
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• 2007

Serotonin (5-HT), the endogenous nonselective 5-HT receptor agonist, activates the inositol-1,4,5-triphosphate/calcium $(InsP3/Ca^{2+})$ signaling pathway and exerts both stimulatory and inhibitory actions on cAMP production and neuromodulin secretion in rat hypothalamic neurons. Specific mRNA transcripts for 5-HT1A, 5-HT2C and 5-HT4 were identified in rat hypothalamic neurons. These experiments were supported by combined techniques such as cAMP and a $Ca^{2+}$ assays in order to elucidate the associated receptors and signaling pathways. The cAMP production and neuromodulin release were profoundly inhibited during the activation of the Gi-coupled 5-HT1A receptor. Treatment with a selective agonist to activate the Gq-coupled 5-HT2C receptor stimulated InsP3 production and caused $Ca^{2+}$ release from the sarcoplasmic reticulum. Selective activation of the Gs-coupled 5-HT4 receptor also stimulated cAMP production, and caused an increase in neuromodulin secretion. These findings demonstrate the ability of 5-HT receptor subtypes expressed in neurons to induce neuromodulin production. This leads to the activation of single or multiple G-proteins which regulate the $InsP3/Ca^{2+}/PLC-{\gamma}$ and adenyl cyclase / cAMP signaling pathways.

• 한국동물생명공학회지
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• 제38권2호
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• pp.77-83
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• 2023

Background: Serotonin receptors can be divided into seven different families with various subtypes. The serotonin 1A (5-HT1A) receptor is one of the most abundant subtypes in animal brains. The expression of 5-HT1A receptors in the brain has been reported in various animals but has not been studied in horses. The 5-HT1A receptor functions related to emotions and behaviors, thus it is important to understand the functional effects and distribution of 5-HT1A receptors in horses to better understand horse behavior and its associated mechanism. Methods: Brain samples from seven different regions, which were the frontal, central, and posterior cerebral cortices, cerebellar cortex and medulla, thalamus, and hypothalamus, were collected from six horses. Western blot analysis was performed to validate the cross-reactivity of rabbit anti-5-HT1A receptor antibody in horse samples. Immunofluorescence was performed to evaluate the localization of 5-HT1A receptors in the brains. Results: The protein bands of 5-HT1A receptor appeared at approximately 50 kDa in the frontal, central, and posterior cerebral cortices, cerebellar cortex, thalamus, and hypothalamus. In contrast, no band was observed in the cerebellar medulla. Immunofluorescence analysis showed that the cytoplasm of neurons in the cerebral cortices, thalamus, and hypothalamus were immunostained for 5-HT1A receptors. In the cerebellar cortex, 5-HT1A was localized in the cytoplasm of Purkinje cells. Conclusions: In conclusion, the study suggests that 5-HT and 5-HT1A receptor systems may play important roles in the central nervous system of horses, based on the widespread distribution of the receptors in the horse brain.

• Biomolecules & Therapeutics
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• 제1권1호
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• pp.77-83
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• 1993

Serotonin (5-hydroxytryptamine, 5-HT) has been known to have peripheral actions as well as central actions. Recently physiological roles of 5-HT as a central neurotransmitter have been studied in detail and this is a subject of the present study. Plausible central actions mediated by 5-HT receptor seem to be a control of appetite, bring about psychiatric disorders such as anxiety or dementia, and migraine headache. In this study, thirty-five medicinal plants were tested for their antagonistic activities to 5-HT mediated actions. Through the preliminary screening, methanol extracts of three medicinal plants (Saussureae Radix, Sanguisorbae Radix and Xanthii Fructus) were shown to possess relatively specific antagonistic activities to 5-HT mediated ileal contraction over acetylcholine. To luther investigate the central antagonistic activities of the selected plant in vivo, m-chlorophenylpiperazine (mCPP) which is known to be a 5-H $T_{1c}$ receptor agonist was injected to mouse to induce an anxious and/or hypolocomotion states, and also social interaction test, which was based on the method described by File (S.E. File, 1980), was performed to see whether ethylacetate fraction of Sanguisorbae Radix methanol extract possessed a specific anxiolytic activity.y.

• Journal of mucopolysaccharidosis and rare diseases
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• 제2권2호
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• pp.43-45
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• 2016

Whole body energy balance is achieved through the coordinated regulation of energy intake and energy expenditure in various tissues including liver, muscle and adipose tissues. A positive energy imbalance by excessive energy intake or insufficient energy expenditure results in obesity and related metabolic diseases. Although there have been many obesity treatment trials aimed at the reduction of energy intake, these strategies have achieved only limited success because of their associated adverse effects. Serotonin is among those traditional pharmacological targets for anti-obesity treatment because central 5-HT functions as an anorexigenic neurotransmitter in the brain. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. However, recent studies suggest the new functions of peripheral serotonin in energy homeostasis ranging from the endocrine regulation by gut-derived serotonin to the autocrine/paracrine regulation by adipocyte-derived serotonin. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Fat specific Tph1 knock-out (Tph1 FKO) mice exhibit similar phenotypes as mice with pharmacological inhibition of 5-HT synthesis, suggesting the localized effects of 5-HT in adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure in BAT and Htr2a KO mice exhibit the decreased lipid accumulation in WAT. These data suggest the clinical significance of the peripheral serotonergic system as a new therapeutic target for anti-obesity treatment.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제12권2호
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• pp.165-178
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• 2001

주의력결핍 ${\cdot}$ 과잉운동장애(이하 ADHD라 기술함)의 생화학적인 원인을 규명하고 개체발생적인 과정에 대한 이해를 하기 위하여 46명의 ADHD아동들과 18명의 발달성언어장애 아동들을 대상으로 혈장내 의 5-HT와 5-HIAA 함량을 측정하고 개체발생적인 과정에 대한 연구를 시행한 결과 다음과 같은 결과를 얻었다. 1) 대상군과 대조군에서 혈장 5-HT(serotonin) 함량비교에서는 혼합형(combined type)은 평균치 17.81 ng/ml, 주의력결핍형은 22.00ng/ml, 과잉운동 ${\cdot}$ 충동형은 24.75ng/ml 대조군의 평균치는 31.83 ng/ml로서 분산분석 결과 의미있는 차이가 관찰되었으며(F=4.33, df 3, 60, p<0.05), Scheffe씨법을 이용한 사후검증에서는 혼합형과 대조군간에는 의미있는 차이가 관찰되었으나 나머지 군간에는 의미있는 차이가 관찰되지 않았다. 2) 대상군과 대조군에서 혈장 5-HIAA함량 비교에서는 의미있는 차이가 관찰되지 않았다(F=2.08, df 3, 60, p>0.05). 3) ADHD전체군과 대조군간의 5-HT 및 5-HIAA함량비교에서는 5-HT함량의 평균치는 21.74ng/ml 이었으며, 대조군의 평균치는 31.83ng/ml로서 의미있는 차이가 관찰되었다(T=3.10, df 62, p<0.05). 그러나, 5-HIAA함량치는 의미있는 차이가 없었다(T=1.90, df 62, p>0.05). 4) ADHD군에서 TOVA소견과 5-HT 및 5-HIAA 함량간의 상관성에 있어서는 의미있는 상관성이 관찰되지 않았다. 5) ADHD군에서 DSM-IV소견과 5-HT 및 5-HIAA함량간의 상관성에 있어서도 의미있는 상관성은 관찰되지 않았다. 6) 대상군과 대조군에서 혈장 5-HT(serotonin)함량과 연령간의 상관성에 있어서는 모두 의미있는 상관성은 관찰되지 않았다(ADHD군：Pearson 상관계수 -0.20, 대조군：-0.05, 모두 p>0.05). 7) 대상군과 대조군에서 혈장 5-HIAA함량과 연령간의 상관성에 있어서도 모두 의미있는 상관성은 관찰되지 않았다(ADHD군：Pearson 상관계수 -0.17, 대조군：0.04, 모두 p>0.05). 이러한 소견으로 미루어 5-HT의 농도저하가 ADHD의 원인중의 일부로 작용할 가능성이 있으며, 5-HT 의 개체발생적인 측면에 있어서는 이상소견이 없을 가능성이 있다. 향후 생화학적인 소견에 의한 아형으로의 분류가 가능할 것으로 생각되면 이러한 분류에 의하여 약물에 대한 반응, 가족력의 차이 또는 예후에 대한 연구가 시행되어야 한다.

• 생명과학회지
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• 제20권10호
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• pp.1451-1457
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• 2010

Serotonin (5-hydroxytryptamine (5-HT))는 신경계의 세포-세포 간의 신호전달의 주요한 신경전달물질이다. 세포막에 존재하는 serotonin transporter (SERT)는 연접간격에 존재하는 5-HT를 세포 내로 재흡수 하여 세포외부의 5-HT 농도를 조절하지만 그 기전은 아직 밝혀지지 않았다. 본 연구에서는 yeast two-hybrid system을 사용하여 SERT의 C-말단이 protein kinase C-$\varepsilon$ (PKC-$\varepsilon$)과 특이적으로 결합함을 알았다. PKC-$\varepsilon$는 PKC의 isotype으로 calcium 비의존적이며 phorbol ester/diacylglycerol 민감성 serine/threonine kinase이다. $Na^+/Cl^-$ 의존성 SLC6 gene family의 다른 수송체는 PKC-$\varepsilon$과 결합하지 않았다. Deletion mutant들을 사용하여 SERT는 PKC-$\varepsilon$의 C-말단부위와 결합함을 알았으며, 또한 이 단백질간의 결합을 GST pull-down assay로 확인하였다. PKC-$\varepsilon$는 in vitro에서 SERT의 N-말단의 펩티드를 인산화시켰다. 이러한 결과들은 PKC-$\varepsilon$에 의한 SERT의 인산화가 세포막에 존재하는 SERT의 활성을 조절하는 역할을 할 가능성을 시사한다.

• 대한수의학회지
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• 제56권4호
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• pp.205-208
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• 2016

The aim of the present study is to investigate the potential influence of obesity as a factor in 5-hydroxytryptamine (5-HT) concentration in myxomatous mitral valve disease (MMVD) dogs. Fifty-five client-owned dogs were enrolled in a randomized trial. Dogs were classified by echocardiography into healthy (control), mild, and moderate to severe MMVD groups. Each group was subclassified by using a 9-point body condition score (BCS); lean (BCS 5-6/9) and obese groups (BCS 7.5-9/9). Dogs with moderate to severe MMVD had lower serotonin (5-HT) concentrations than the control group (p = 0.03). Dogs with moderate to severe MMVD (p = 0.017) had lower serum 5-HT concentrations than the control group in the obese group (BCS 7.5-9/9). Significant difference was found between the lean and obese groups (p = 0.015) which are not consider severe in the MMVD group. These results suggested that 5-HT concentration was decreased with the increasing severity of MMVD, and obesity might be taken into consideration when interpreting the serotonin concentration in MMVD dogs.

• 통합자연과학논문집
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• 제11권2호
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• pp.87-92
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• 2018

5-Hydroxytryptamine receptor 7 ($5-HT_7R$) is one of G-Protein coupled receptors, which is found to be involved in the pathophysiology of various neurological disorders including depression, sleep disorders, memory deficiency and neuropathic pain. After activation of $5-HT_7R$ by serotonin, it activates the production of the intracellular signaling molecule cyclic AMP. The availability of 3D structure of the receptor would enhance the development of new drugs. Hence, in the present study, homology modelling of human 5-hydroxytryptamine receptor 7 ($5-HT_7R$) was performed using comparative modelling (Easy Modeller) and threading (I-TASSER) approaches. The generated models were validated using Ramachandran plot and ERRAT plot and the best models were selected based on the validation results. The 3D model developed here could be useful for identifying crucial residues and further docking study.

• 한국응용곤충학회지
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• 제43권2호
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• pp.155-162
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• 2004

세로토닌 수용체는 세로토닌과 반응하여 세포막의 G단백질을 통해 중개단백질 (adenylyl cyclase, phospholipase C, cGMP phosphodiesterase, ion channel)을 활성화시켜, 이뇨, 기억, 발생 등의 다양한 생리적 반응에 관여한다. 곤충세포인 Schneider2 (S2)와 척추동물 세포인 Chinese hamster ovary (CHO)-Kl에서 Aedes 5-HT$_{7}$ 수용체 유전자 발현을 비교하기 위해, Aedes 5-HT$_{7}$ 수용체 유전자를 형질이입시켰다. 선발된 세포주들(Tr-S2, Tr-CHO)에서 세로토닌 수용체 유전자의 발현은 reverse transcription-PCR, Western blot, immunocytochemistry를 이용하여 확인하였다. 세로토닌 농도증가에 대한 Aedes 5-HT$_{7}$수용체의 기능을 세포 내 cAMP수준을 통해 조사한 결과,Tr-CHO 세포주는 Tr-S2 세포주보다 9배 이상 cAMP수준이 높게 나타났으며, 농도에 의존적이었다. 이 결과는 수용체 유전자가 세포에서 발현되었으나, 세포의 종류와 세포막에 존재하는 G단백질 차이에 따라 중개단백질 활성 차이가 있다는 것을 보여주었다. CHO-Kl 세포에서 Aedes 5-HT$_{7}$ 수용체의 기능이 S2 세포보다 더 효율적이며, Aedes 5-HT$_{7}$ 수용체를 발현하는 Tr-CHO 세포주는 동력제 또는 대립제 검정에 활용될 수 있을 것으로 기대된다. 것으로 기대된다.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.7-18
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• 1996

5-Hydroxytryptamine(5-HT, serotonin), when given into the vein, produced antidiuretic action accompanied with reduction of glomerular filtration(GFR), renal plasma flow(RPF), osmolar clearance(Cosm) and amounts of sodium or potassium excreted in urine( $E_{Na}$ , $E_{K}$), with the augmented reabsorption rates of sodium and potassium in renal tubules. 5-HT, when infused into a renal artery, exhibited diuretic action accompanied with the augmented RPF and increased $E_{Na}$ and $E_{K}$ in only infused kidney. Antidiuretic action of 5-HT infused into the vein was not influenced by ketanserin, 5-H $T_2$receptor blockade, given into a renal artery, vein or carotid artery, by methysergide, 5-H $T_1$receptor blockade, given into a renal artery, whereas above antidiuretic action was inhibited by methysergide given into vein or carotid artery. Diuretic action of 5-HT infused into a renal artery in only experimental kidney was blocked by ketanserin injected into a renal artery, was not influenced by methysergide administered into a renal artery. Above results suggest that 5-hydroxytryptamine(5-HT) produced the antidiuretic action through central 5-H $T_1$receptor and the diuretic action through 5-H $T_2$receptor located in renal tubules of kidney.ney.