• Biomolecules & Therapeutics
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• 제31권2호
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• pp.176-182
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• 2023

Among 14 subtypes of serotonin receptors (5-HTRs), 5-HT_2AR plays important roles in drug addiction and various psychiatric disorders. Agonists for 5-HT_2AR 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-HT_2AR 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-HT_2AR 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-HT_2AR, 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-HT_2AR, suggesting their agonistic nature. In conclusion, this study provides information for designing novel ligands for 5-HT_2AR, which can be used to control psychiatric disorders and drug abuse.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 춘계학술대회
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• pp.102-102
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• 1997

The purpose of this study was to determine the behavioral interaction between glutamatergic and serotonergic receptors. In the present study, both the competitive (AP-5 and D-CPP) and the noncompetitive (MK-801, ketamine, dextrorphan and dextromethorphan) N-methyl-D-aspartate (NMDA) receptor antagonists markedly enhanced 5-HT(5-hydroxytryptamine)-induced selective serotonergic behavior, head-twitch response (HTR), in mice. These results suggest that the glutamatergic neurotransmission may modulate serotonergic function at the 5-HT receptor. The precise relationship between glutamatergic and serotonergic system is as yet undefined. However, these are the first data available regarding glutamatergic modulation of serotonergic function at the 5-HT receptor in intact mice, and the present results support the notion that the NMDA receptors may play important roles in the glutamatergic modulation of serotonergic function at the 5-HT receptor.

• Journal of Life Science
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• 제9권2호
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• pp.82-85
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• 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.

• Archives of Pharmacal Research
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• 제13권1호
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• pp.55-63
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• 1990

An attempt was made to investigate the effect of intracerebroventricular 5-hydroxytrypatamine (5-HT) on the cardiovascular system in urethane-anesthetized rabbit and to elucidate the mechanism of its action. 5-HT given into a lateral ventricle caused clearly a dose-dependent decrease inboth arterial blood pressure and in heart rate. The bradycardia and hypotension induced by 5-HT were significantly attenuated by the prior injection of ketanserin, cyproheptadine or clonidine. Pretreatment of atropine with bilateral vagotomy did not affect both bradycardia and hypotension. Propranolol weakened markedly the breadcardia of 5-HT but did not influence the depressor response of 5-HT. These experimental results suggest that intraventricular 5-HT cause the hypotension and bradyardia in rabbits through the stimulation of serotonergic receptors in brain, which is seemed to be associated to inhibition of sympathetic tone.

• 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.

• The Journal of Korean Physical Therapy
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• 제23권1호
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• pp.59-66
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• 2011

Purpose: The purpose of this study was to investigate the effect of electroacupuncture on pain threshold and 5-HT synthesis in raphe magnus nucleus of dog brain stem following nociception induced by 1% carageenan. Method: Twenty male dogs were randomly divided into two groups, a control group and an electroacupuncture group with the following parameters: ST36, LI11 and SP9 with 120Hz and 0.5mA. The dogs were sacrificed at 30, 60, 90, 120, 150 and 180 min after nociception using 1% carageenan injection into the plantar side of the dog's left leg. The pain threshold was recorded by an Analgesia-meter. After making brain slice sections, the tissues were immunostained with 5-HT antisera (1:2,500). Results: The pain threshold for the electroacupuncture group was higher than for the control group. The number of 5-HT immunoreactive neurons in the electroacupuncture group was greater than that of the control group. Differences between the two groups regarding the number of 5-HT immunoreactive neurons at 30 min and 60 min (p<0.05), at 120 min and 150 min (p<0.01), and at 8 days (p<0.05) were significant. Conclusion: The increases in pain threshold and number of 5-HT immunoreactive neurons in the raphe magnus nucleus of dog brain stem showed that electroacupuncture can attenuate pain transduction through the descending tract.

• Journal of Ginseng Research
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• 제29권1호
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• pp.37-43
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• 2005

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human $5-HT_{3A}$ receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

• Journal of Acupuncture Research
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• 제21권6호
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• pp.51-62
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• 2004

Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/kg, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.221-221
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• 1996

(중략) 1)에탄올 0.08g/kg 급성투여군은 선조체 5-HT, DOPAC, HVA, DOPAC/DA, HVA/DA ratio를 현저히 증가시켰다. 반면, 3g/kg 급성투여군은 도파민 및 세로토닌 신경활성에 전혀 영향을 미치지 않았다. 2) 에탄을 3g/kg을 21회 연속투여군은 선조체 DA 및 5-HT와 5-HIAA 함량을 유의성있게 증가하였으나 도파민 대사산물에는 영향을 주지 않았다. 3) 35주령 흰쥐는 에탄을 3g/kg 급성투여군에서 5-HT함량을 감소시켰으나 3g/kg 21회 연속투여군은 5-HT함량을 유의성있게 증가시켰다. 4) 7주령과 35주령 모두 21회 연속투여에서 DA 및 5-HT함량을 현저히 증가시켰다.

• Applied Microscopy
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• 제18권2호
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• pp.59-76
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• 1988

In order to know the distribution, relative frequencies, types and morphology, endocrine cells in the intestinal tract of the hedgehog(Erinaceus koreanus) were studied by light microscopy, immunohistochemistry and electron microscopy. The results obtained are summarized as follows: 1. Two kinds of endocrine cells were demonstrated with two specific staining methods. Argyrophil cells(reactive cells for Grimelius method) were found most frequently in the intestinal region, and were infrequent in the rectum, whereas argentaffin cells (reactive cells for Masson-Hamperl method) were found most frequently in the rectum and in the other legions were infrequent. These reacting cells were mainly found in the intestinal glands, whereas a small number in the mucosa. 2. Twelve kinds of endocrine cells, gastrin(Gas)-, somatostatin (Som)-, serotonin(5-HT)-, glucagon(Glu)-, bovine pancreatic polypeptide(Bpp)-, cholecystokinin(Cck)-, secretin(Sec)-, motilin(Mot)-, glicentin(Gli)-, gastric inhibitor polypeptide(GIp)-, substance P(Sp)-, and neurotensin(Neu)-immunoreactive cells, were identified by immunohistochemical method. Gas-, Som-, 5-HT-, Glu-, Cck-, Sec-, Mot-, Gli-, Sp-, and Neu-reactive cells were observed in the duodenum, and among these Gas- and 5-HT-reactive cells were moderately found while the others were infrequent. In the jejunoileum Gas-, Som-, 5-HT-, Glu-, Cck-, Mot-, Gli-, GIp-, SP-, and Neu-reactive cells were found, and among these 5-HT- and GIp-reactive cells were moderately found while the others were infrequent. In the colon Sec-reactive cell was not detected. 5-HT-reactive cells were found most frequently and the others were infrequent in this region. 5-HT-, Bpp-, GIi- and Neu-reactive cells were found in the rectum. Among these 5-HT-reactive cells were found most frequently. 3. Electron microscopically, five types of endocrine cells, EC, ECL, D, G, A-like cell, were identified in the intestinal region. EC and ECL cells in the duodenum, EC, D and G cells in the jejuno-ileum, EC and A-like cells in the colon and EC cell in the rectum were observed respectively.