• Archives of Pharmacal Research
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• v.22 no.2
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• pp.113-118
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• 1999

Previous work in our laboratory has shown that the N-methyl-D-aspartate (NMDA) receptor antagonists, AP-5, CPP, MK-801, ketamine, dextrorphan and dextromethorphan cause a pronounced enhancement of 5-hydroxytryptamine (5-HT)-induced head-twitch response (HTR) in intact mice, suggesting the involvement of NMDA receptors in the glutamatergic modulation of serotonergic function at the postsynaptic $5-HT_{2}$ receptors. The purpose of this study was to extend our previous work on the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both competitive (AP-5 and CPP) and noncompeti-tive (MI-801, ketamine, dextrorphan and dextromethorphan) NMDA receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, in p-chlorophenylalanine (PCPA)-treated mice which were devoid of any involvement of indirect serotonergic function, to establish the involvement of the NMDA receptor in 5-HT-induced HTR at the postsyaptic $5-HT_{2}$receptors. In addition, the enhancement of 5-HT-induced HTR was inhibited by a dopamine agonist, apomorphine, NMDA receptor antagonist, NMDA and a serotonin $5-HT_{2}$receptor antagonist, cyproheptadine, in PCPA-treated mice. Therefore, the present results support our previous conclusion that the NMDA receptors play an important role in the glutamatergic modulation of serotonergic function at the poststynaptic $5-HT_{2}$ receptors.

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.137-146
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• 1992

The central tryptaminergic system has been shown to play an important role in the regulation of renal function: $5-HT_1$ receptor mediate diuresis and natriuresis, whereas both $5-HT_2$ and $5-HT_3$ mediate antidiuresis and antinatriuresis. Recently, $5-HT_1$ receptors are further subdivided into many subtypes, and central $5-HT_{1A}$ subtype was shown to mediate diuretic and natriuretic effects. The present study was undertaken to delineate the role of $5-HT_{1B}$ subtype. Trifluoromethylphenylpiperazine (TFMPP), a selective $5-HT_{1B}$ agonist in doses ranging from 8 to $750\;{\mu}g/kg$ icv elicited diuresis, natriuresis and kaliuresis in dose-dependent fashion, with the fractional excretion of filtered Na reaching 5.44% with $250\;{\mu}g/kg$ icv. The natriuresis outlasted the transient increases in renal hemodynamics, suggesting humoral mediation in the decreased tubular Na reabsorption. Plasma concentration of atrial natriuretic peptide increased along with the natriuresis. Systemic blood pressure transiently increased. When given intravenously, no diuresis and natriuresis was elicited, indicating the central mechanism. The icv TFMPP effects were not significantly affected by icv methysergide, a nonselective $5-HT_1$ blocker. Both ketanserin and MDL 72222, selective $5-HT_2$ and $5-HT_3$ antagonists, resp., did not abolish the TFMPP effects. Nor did NAN-190, $5-HT_{1A}$ blocker, affect the TFMPP effects. These observations suggest that central $5-HT_{1B}$ receptors may play a role in the central regulation of renal function by exerting diuretic and natriuretic influences, mainly through natriuretic factors.

• Journal of Animal Science and Technology
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• v.64 no.5
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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.

• BMB Reports
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• v.56 no.10
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• pp.527-536
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• 2023

Serotonin receptors, also known as 5-HT receptors, belong to the G protein-coupled receptors (GPCRs) superfamily. They mediate the effects of serotonin, a neurotransmitter that plays a key role in a wide range of functions including mood regulation, cognition and appetite. The functions of serotonin are mediated by a family of 5-HT receptors including 12 GPCRs belonging to six major families: 5-HT₁, 5-HT₂, 5-HT₄, 5-HT₅, 5-HT₆ and 5-HT₇. Despite their distinct characteristics and functions, these receptors' subtypes share common structural features and signaling mechanisms. Understanding the structure, functions and pharmacology of the serotonin receptor family is essential for unraveling the complexities of serotonin signaling and developing targeted therapeutics for neuropsychiatric disorders. However, developing drugs that selectively target specific receptor subtypes is challenging due to the structural similarities in their orthosteric binding sites. This review focuses on the recent advancements in the structural studies of 5-HT receptors, highlighting the key structural features of each subtype and shedding light on their potential as targets for mental health and neurological disorders (such as depression, anxiety, schizophrenia, and migraine) drugs.

• The Korean Journal of Pharmacology
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• v.17 no.2
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• pp.47-62
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• 1981

d-amphetamine이 사람에서 paranoid schizophrenia와 아주 유사한 model psychosis를 일으키며 또한 사람과 실험동물에서 실제 정신분열증에서 뚜렷이 관찰되는 behavioral perservation을 일으킬 수 있음이 관찰되었다. 이에 많은 학자들은 이러한 양상의 행동변화가 정신분열증의 원인 추구에 중요한 의미를 주는 뇌변화를 반영할지도 모른다는 생각에 많은 연구를 거듭하여 왔다. 지금까지는 주로 catecholamine기전에 대하여 집중적 연구가 수행되어져 왔으나 최근에는 d-amphetamine의 약리기전의 일부는 5-HT기전이 차지하고 있으며, 여러 행동변화에는 catecholaimin 보다 5-HT 가 더 중요하게 관계하고 있다는 주장이 나오고 있다. 또한 d-amphetamine은 시험관내에서 MAO 특히 신경전달물질 분해요소인 A type를 가역적으로 억제할 수 있음이 보고되어 많은 흥미를 끌어왔으나 생체내에서의 억제여부는 직접적으로 확인이 되고 있지 않다. 그러나 최근에 Braestrup(1977)과 El Hait(1978)등은 간접적인 방법으로 생체내에서도 억제시킬 수 있음을 보고하고 있다. 이에 저자는 d-amphetamine에 의해 야기되는 행동변화와 그 밑바탕을 이루는 생화학적 기전에 5-HT가 차지하는 역할을 알아보기 위해서 다음의 실험을 시행하였다. 첫째, d-amphetamine의 급성, 만성 투여가 5-HT의 5-HIAA 로의 turnover와 MAO활성도에 어떤 영향을 미치며, 더 나아가서 이 양자사이에 어느 정도 상관관계가 있는지를 알아보기 위해서 d-amphetamine을 투여한 후 시간 경과에 따라서 뇌내 5-HT, 5-HIAA, 5-HT turnover rate와 MAO 활성도를 측정하였다. 둘째, d-amphetamine, 5-HT 합성을 증가시키는 약물과 합성을 억제시키는 약물을 투여하고, 위의 생화학적 실험과 행동관찰을 병합 실시하여 비교분석하였다. 그 결과는 다음과 같다. 1) d-amphetamine (6 mg/kg)을 급성투여시, 뇌내 5-HT함량이 투여 1시간 후에 최고로(대조치의 123%, p<0.001) 증가되다가 이후 감소하며, 5-HIAA 함량은 처음 15분부터 감소하기 시작하다가 30분에 최저로 떨어지며(대조치의 78%, p<0.005) 이후 증가하여 24시간째는 약간 대조치 이상으로 회복되었다. 미토콘드리아 MAO활성도는 1시간째에 최저로 떨어지다가(대조치의 89%, p<0.05)이후 회복하기 시작하여 24시간째에 약간 대조치 이상으로 회복되었다. 5-HT의 turnover rate는 MAO활성도 변화와 거의 같은 변화를 보였다. 2) 만성투여시 (하루 2번, 14일간 투여)는 5-HT 함량, 5-HIAA 함량, MAO 활성도 및 5-HT turnover rate 모두가 중등도로 감소되었다. (각각 대조치의 87%, 69%, 80%, 79%). 3) MAO 활성도와 5-HT turnover rate 사이에는 높은 상관관계가 있었다. (r=0.866, p<0.001, N=94). 4) MAO 활성도의 역동학 실험에서는 대조치에 비해 투여군에서 Km 값은 의미가 있는 증가가 있었으나 $V_{max}$값은 큰 변동이 없었다. 5) d-amphetamine을 급성 투여할때는 sleeping과 lying components는 상당한 감소를 보인 반면, locomotor activity 는 1시간까지는 상당한 증가를 보였으며 용량이 적을수록 더 큰 증가가 있었다. 반면 stereotypy는 1시간까지 용량이 증가할수록 더 큰 증가가 나타나서 locomotor activity에서 stereotypy 의 증가로 이행을 나타내었다. 만성 투여시는 locomotor activity는 점차적인 감소를 보였으나 stereotypy는 점차적인 증가가 나타나서 14일쯤에는 평형에 도달하였다. 6) PCPA 단독 투여군(400 mg/kg, 3번)에 있어서는 5-HT와 5-HIAA 함량의 상당한 감소가 나타났으나 MAO 활성도와 행동에는 큰 변화를 나타내지 않았다. PCPA전 처치군에 있어서도 5-HT와 5-HIAA 함량은 마찬가지로 상당한 감소를 나타내었으나 gnawing, sniffing과 locomotor activity는 더 증가를, stereotyped head weaving, forepaw treading과 hindlimb abduction은 상당한 감소를 나타내었다. 7) L-tryptophan(100 mg/kg)단독 투여시는 5-HT 함량은 약간 증가를 나타내었으나 5-HIAA 함량은 상당한 증가를 보였다. MAO활성도나 행동은 큰 변화없었다. L-tryptophan 전처치군에 있어서는 5-HT 함량은 더 큰 증가를 보였으나, 5-HIaa 함량은 MAO 활성도는 별 변화없었으며 stereotypedlateral head waving, forepaw treading 과 hindlimb abduction은 증가를, locomotor activity, gnawing과 sniffing components는 감소를 나타내었다. 8) d-amphetamine 단독투여, 혹은 L-tryptophan 전처치, PCPA 전처치후 측정한 5-HT 함량과 stereotyped head weaving, forepaw treading, hinilimb abduction components 사이에는 높은 상관관계가 있었다(r=0.789, p<0.001). 반면 5-HT 함량과 locomotor activity, stereotyped gnawing과 sniffing components 사이에는 약한 음성의 상관관계가 있었다. (r=0.554, p <0.005). 이상의 결과로 미루어 볼때 5-HT의 5-HIAA 로의 turnover rate 는 주로 MAO 활성도에 의해서 조절되며 5-HT 기전이 d-amphetamine에 의해서 야기된 여러 행동변화 중 상당한 부분에서 중요한 역할을 하리라고 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.1
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• pp.65-70
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• 2012

Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

• Biomolecules & Therapeutics
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• v.4 no.1
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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.

• Molecules and Cells
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• v.40 no.7
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• pp.495-502
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• 2017

The $5-HT_6R$ has been considered as an attractive therapeutic target in the brain due to its exclusive expression in the brain. However, the mechanistic linkage between $5-HT_6Rs$ and brain functions remains poorly understood. Here, we examined the effects of $5-HT_6R$-mediated cell morphological changes using immunocytochemistry, Western blot, and live-cell imaging assays. Our results showed that the activation of $5-HT_6Rs$ caused morphological changes and increased cell surface area in HEK293 cells expressing $5-HT_6Rs$. Treatment with 5-HT specifically increased RhoA-GTP activity without affecting other Rho family proteins, such as Rac1 and Cdc42. Furthermore, live-cell imaging in hippocampal neurons revealed that activation of $5-HT_6Rs$ using a selective agonist, ST1936, increased the density and size of dendritic protrusions along with the activation of RhoA-GTP activity and that both effects were blocked by pretreatment with a selective $5-HT_6R$ antagonist, SB258585. Taken together, our results show that $5-HT_6R$ plays an important role in the regulation of cell morphology via a RhoA-dependent pathway in mammalian cell lines and primary neurons.

• Food Science and Preservation
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• v.22 no.4
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• pp.559-566
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• 2015

The aim of this study was to develop an analytical method for determination of T-2 toxin and HT-2 toxin level in cereals and to survey their levels using LC-MS/MS. The T-2 and HT-2 toxins were simultaneously analyzed by electrospray ionization with a positive ion mode and multiple reaction monitoring (MRM) after filteration and immuno-affinity column clean-up. A matrix-matched standard calibration used for quantification and recoveries of T-2 and HT-3 toxins were in the range of $100.6{\pm}7.2%$ and $96.8{\pm}9.4%$, respectively. Limits of detection and quantification of T-2 and HT-2 toxins were estimated to be 0.5 and $1.5{\mu}g/kg$, respectively. Each repeatability (RSRr) of T-2 and HT-2 toxins was determined to be 0.9~6.0%, and 4.9~6.1%, respectively. Total 115 samples cereals were collected from 9 types of cereals for analysis. The positive percentages of T-2 and HT-2 toxins obtained from collected samples were found to be 72% and 80%, respectively. The contamination level of T-2 toxin and HT-2 toxin in cereals were $37.1{\mu}g/kg$, and $5.4{\mu}g/kg$, respectively. Therefore, this study suggests that the developed method could be an useful analytical method to determine the T-2 and HT-2 toxin level in cereals and the present data could be used as a reference to estimate the risk assessment.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.11
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• pp.4455-4458
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• 2014

Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.