• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.39-39
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• 1992

5-Hydroxytryptamine(serotonin, 5-HT)은 중추신경의 신경 전달물질로서 조울병, 불안신경증 등의 정신병태생리에 중요한 역할을 한다. Radioligand 결합실험에 의하여 5-$HT_{1A}$, 5-$HT_{1B}$, 5-$HT_{1C}$, 5-$HT_{1D}$, 5-$HT_{2}$, 5-$HT_3$의 5-HT receptor subtypes의 존재가 확인되어 있고, 그 중에서도 5-$HT_{1A}$ receptor는 중추작용 증 정 도의 조절에 관계가 깊은 raphe nuclei 및 해마에 주로 존재하여 약리학적으로는 체온강하, 혈압 강하, 과식작용, corticosterone 분비 등과 관련되어 있음이 알려져 있다. 따라서 본 수용체 agonist가 항불안약, 항우울약 또는 항고혈압약으로서의 응용이 가능해지면서 5-$HT_{1A}$ 수용체 기능의 해명 및 그 agonist의 개발이 주목받고 있는 가운데, 본 연구에 있어서, 항불안약 개발목적으로 합성된 일련의 화합물 중 1-<3-(3,4-methylene-dioxyphenoxy)propyl> 4-phenyl piperazine (DP-554)이 5-HT 수용체에 특이적이고 선택적으로 높은 친화성을 가지며, rat 해마의 막분획에서 adenylate cyclase 활성을 억제하고, 뇌내 5-HT turnover rate를 감소시키는 둥의 약리학적 작용을 나타내어, 이 화합물이 5-$HT_{1A}$ receptor agonist로서 작용함을 밝혔다. Mouse vas deferens (MVD)를 이용한 실험에서 5-$HT_{1A}$ receptor가 MVD의 교감신경 말단에 존재하여 그 neurotransmission을 억제함이 시사되었으며, 이 조직에서 또한 5-$HT_2$와 5-$HT_3$ 수용체의 존재를 확인하고 각각의 기능을 분명히 했다.

• Journal of Acupuncture Research
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• v.24 no.1
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• pp.111-125
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• 2007

Objection : The aim of this study was to investigate anti-ischemic effect of LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture. Methods : I designed to investigate whether LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture affects cerebral hemodynamics [regional cerebral blood flow(rCBF), pial arterial diameter(PAD), mean arterial blood pressure (MABP) ] in normal and cerebral ischemia rats by MCA occlusion method, and to make manifest whether LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture is mediated by cyclooxygenase or guanylate cyclase. The changes of rCBF and MABP were determinated by laser-doppler flowmetry(LDF), and the change of PAD was determinated by video microscope and width analyzer. Results: The results were as follows ; 1. LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture was significantly increased rCBF, PAD, but decreased MABP after withdrawing of the needle. This results suggest that LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced significantly rCBF by dilating PAD. 2. Pretreatment with indomethacin (1mg/kg, i.v.) was significantly inhibited LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced increase of rCBF and PAD, but increased LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced decrease of MABP after withdrawing of the needle. 3. Pretreatment with methylene blue(10/${\mu}$g/kg, i.v.) was decreased LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced increase of rCBF and MABP, but accelerated LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture induced decrease of PAD. This results suggest that the mechanism of LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture is mediated by cyclooxygenase or guanylate cyclase. Conclusion : I suggest that LR1 ${\cdot}$ HT8 ${\cdot}$ HT9 Reinforcement in Acupuncture has an anti-ischemic effect through the improvement of cerebral hemodynamics, and the mechanism IS mediated by cyclooxygenase.

• Journal of the Korean Applied Science and Technology
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• v.40 no.5
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• pp.988-1000
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• 2023

Hesperetin(HT) is a potent antioxidant flavonoid aglycone derived from hesperidin(HD). The antioxidant, anti-inflammatory, and antimicrobial activities of HT and its cyclodextrin(CD) inclusion complexes were compared in vitro. HT was prepared by enzymatic hydrolysis of HD, and HT/CD complexes were prepared using 𝛽-cyclodextrin(𝛽-CD) and hydroxypropyl-𝛽-cyclodextrin(HP-𝛽-CD) by solvent co-evaporation method. The solubility of the HT/HP-𝛽-CD inclusion complex increased 93.5-fold compared to HT, and the solubility of HT/𝛽-CD increased 22.5-fold. The HT/HP-𝛽-CD inclusion complex showed a similar effect as HT on radical scavenging activity in antioxidant assays, whereas the HT/𝛽-CD inclusion complex showed slightly lower activity than HT. Cytotoxicity was low in the following order; HT/HP-𝛽-CD, HT/𝛽-CD, and HT in murine macrophage RAW264.7 cells. Treatment with HT and HT/CD inclusion complexes reduced the levels of inflammatory mediators such as nitric oxide(NO), tumor necrosis factor-𝛼(TNF-𝛼) and interleukin-6(IL-6) in the cells. HT and HT/HP-𝛽-CD inclusion complex were more effective than HT/𝛽-CD inclusion complex at relatively low concentrations. Inhibitory effects were tested on skin-pathogenic bacteria, Staphylococcus aureus and Pseudomonas aeruginosa, and they showed an antimicrobial effect on S. aureus in the order of HT = HT/HP-𝛽-CD > HT/𝛽-CD, but they did not show any significant inhibitory effect on P. aeruginosa. In conclusion, HT, the aglycone form of HD, and its CD inclusion complexes showed various biological activities. HT/HP-𝛽-CD inclusion complex, which is the highly soluble form of HT, showed relatively higher activity compared to HT/𝛽-CD inclusion complex.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.5
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• pp.267-272
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• 2011

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the $5HT_2$ receptor antagonist ketanserin and the $5-HT_3$ receptor antagonist ondansetron but was inhibited by the 5-$HT_1$ receptor antagonist methysergide and 5-$HT_4$ receptor antagonist GR113808. These results indicate that 5-$HT_1$ and 5-$HT_4$ receptors may mediate the contraction of the 5-HT-induced response and 5-$HT_2$ and 5-$HT_3$ receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.169-177
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• 2017

Lamotrigine is an antiepileptic drug widely used to treat epileptic seizures. Using whole-cell voltage clamp recordings in combination with a fast drug application approach, we investigated the effects of lamotrigine on 5-hydroxytryptamine $(5-HT)_3$ receptors in NCB-20 neuroblastoma cells. Co-application of lamotrigine ($1{\sim}300{\mu}M$) resulted in a concentration-dependent reduction in peak amplitude of currents induced by $3{\mu}m$ of 5-HT for an $IC_{50}$ value of $28.2{\pm}3.6{\mu}M$ with a Hill coefficient of $1.2{\pm}0.1$. These peak amplitude decreases were accompanied by the rise slope reduction. In addition, $5-HT_3$-mediated currents evoked by 1 mM dopamine, a partial $5-HT_3$ receptor agonist, were inhibited by lamotrigine co-application. The $EC_{50}$ of 5-HT for $5-HT_3$ receptor currents were shifted to the right by co-application of lamotrigine without a significant change of maximal effect. Currents activated by 5-HT and lamotrigine co-application in the presence of 1 min pretreatment of lamotrigine were similar to those activated by 5-HT and lamotrigine co-application alone. Moreover, subsequent application of lamotrigine in the presence of 5-HT and 5-hydroxyindole, known to attenuate $5-HT_3$ receptor desensitization, inhibited $5-HT_3$ receptor currents in a concentration-dependent manner. The deactivation of $5-HT_3$ receptor was delayed by washing with an external solution containing lamotrigine. Lamotrigine accelerated the desensitization process of $5-HT_3$ receptors. There was no voltage-dependency in the inhibitory effects of lamotrigine on the $5-HT_3$ receptor currents. These results indicate that lamotrigine inhibits $5-HT_3$-activated currents in a competitive manner by binding to the open state of the channels and blocking channel activation or accelerating receptor desensitization.

• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.282-282
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• 1994

Radioligand결합실험에 의하여 7가지 이상의 5-hydroxytryptamine serotonin, 5-HT)수용체 subtype가 규명되어 있고, 1983년 5-HT agonist로 알려져 있던 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)가 〔$^3$H〕5-HT수용체에 대한 결합만을 선택적으로 억제하며, 본 수용체를 직접 표식함이 알려진 이래, 본 수용체의 기능에 대한 연구가 계속되어 오고있다. 특히 항불안약으로 임상에 사용되어 왔던 benzodiazepines이 5-HT neuron의 활성을 억제한다는 사실이 보고되면서 5-HT neuron과 불안과의 관련에 관한 연구가 계속되고 있는 가운데, 새로운 항불안약으로 주목을 받고 있던 buspirone이 5-$HT_{1A}$ 수용체에 높은 친화성을 가짐이 확인되었다. 그 외에도 5-$HT_{1A}$ 수용체작용약이 항우울약, 항고혈압약으로서의 응용가능성 이 시사되면서 본 수용체작용약의 개발 및 그 기능해명이 주목을 받고 있다. 본 연구에서는, 5-$HT_{1A}$ 수용체작용약인 8-OH-DPAT와 항불안약을 개발할 목적으로 합성된 화합물인 1-[3-(3,4-methylenedioxyphenoxy)propy〕-4-phenyl piperazine (8P-554)을 이용하여, 화합물의 5-HT$_{1A}$수용체에 대한 친화성을 검토하는 방법과. 본 수용체를 통하여 나타난다고 알려져 있는 5-HT의 약리작용을 검토하는 방법을 기술하므로서, 여러가지 임상적 응용을 위하여 새롭게 합성되는 화합물의 5-$HT_{1A}$ 수용체와의 상호작용을 검색하는 방법을 제시하고자 한다.다.

• Journal of Acupuncture Research
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• v.35 no.1
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• pp.28-36
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• 2018

Background: This study investigated the effects of acupuncture at Sobu (HT8) and Haenggan (LR2) on scopolamine-induced, cognitively impaired rats. Methods: Scopolamine-treated Sprague-Dawley rats were divided into 6 groups; normal, control, HT8, LR2, HT8 + LR2 and sham group. Cognitive impairment was induced by scopolamine, in control, and then in HT8, LR2, HT8 + LR2 and sham groups. Acupuncture treatment was performed at HT8, LR2, HT8 + LR2, and a random acupoint, respectively, every other day for 2 weeks. After each treatment, behavior change was observed and the rats were sacrificed. The change in brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase activity was evaluated by polymerase chain reaction. Results: Latency time to target in Morris Water-Maze test for the HT8 + LR2 group showed a significant decrease compared with control (p<0.05). Target crossing times and time zone ratios in Morris Water-Maze test for HT8 + LR2 group showed a significant increase compared with control (p<0.01). In the Y-Maze test the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Brain-derived neurotrophic factor, glutathione peroxidase, and superoxide dismutase, in the HT8 + LR2 group, showed a significantly increased level compared with control (p<0.05). Neural activity of acetylcholine esterase in HT8 + LR2 group showed a significant decrease compared with the control group (p<0.01), choline acetyltransferase activity in the HT8 + LR2 group showed a significant increase compared with control (p<0.05). Conclusion: Acupuncture at HT8 + LR2 restored scopolamine-induced cognitive impairment, suggesting acupuncture could be an alternative to improve cognitive function.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.5
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• pp.419-426
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• 2019

Mosapride accelerates gastric emptying by acting on 5-hydroxytryptamine type 4 ($5-HT_4$) receptor and is frequently used in the treatment of gastrointestinal (GI) disorders requiring gastroprokinetic efficacy. We tested the effect of mosapride on 5-hydroxytryptamine type 3 ($5-HT_3$) receptor currents because the $5-HT_3$ receptors are also known to be expressed in the GI system and have an important role in the regulation of GI functions. Using the whole-cell voltage clamp method, we compared the currents of the $5-HT_3$ receptors when 5-HT was applied alone or was co-applied with mosapride in cultured NCB-20 cells known to express $5-HT_3$ receptors. The $5-HT_3$ receptor current amplitudes were inhibited by mosapride in a concentration-dependent manner. Mosapride blocked the peak currents evoked by the application of 5-HT in a competitive manner because the $EC_{50}$ shifted to the right without changing the maximal effect. The rise slopes of $5-HT_3$ receptor currents were decreased by mosapride. Pre-application of mosapride before co-application, augmented the inhibitory effect of mosapride, which suggests a closed channel blocking mechanism. Mosapride also blocked the opened $5-HT_3$ receptor because it inhibited the $5-HT_3$ receptor current in the middle of the application of 5-HT. It accelerated desensitization of the $5-HT_3$ receptor but did not change the recovery process from the receptor desensitization. There were no voltage-, or use-dependency in its blocking effects. These results suggest that mosapride inhibited the $5-HT_3$ receptor through a competitive blocking mechanism probably by binding to the receptor in closed state, which could be involved in the pharmacological effects of mosapride to treat GI disorders.

• Korean Journal of Biological Psychiatry
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• v.1 no.1
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• pp.88-97
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• 1994

Many evidences are compatible with the correlation between the inhibition of [$^3H$] imipramine([$^3H$]IMI) and [$^3H$]paroxetine([$^3H$]PAT) binding to the 5-hydroxytryptamine(5-HT) transporter complex and the 5-HT uptake of 5-HT neurons and platelets, and most antidepressants have been shown to inhibit the [$^3H$]IMI and [$^3H$]PAT binding and the neuronal 5-HT uptake. However, several paradoxical research findings led to doubt about the pharmacological significance of the [$^3H$]IMI and [$^3H$]PAT binding sites. This study was carried to clarify the correlation between the [$^3H$]IMI and [$^3H$]PAT binding parameters and the tissue 5-HT content or/and [$^3H$]5-HT uptake in the rabbit platelet, which contains 40 times ad much 5-HT as that of human platelet and shows the 10 fold higher $B_{max}$ of the 5-HT transporter binding to a 5-HT uptake inhibitor. The rabbits were treated for 28 days with amitriptyline(4mg/kg/day : AP), fluoxetine(0.5mg/kg/day : FO), and sertraline(0.5mg/kg/day : SA) via an Alzet osmotic pump implanted for constant infusion. The [$^3H$]IMI binding $B_{max}$ and $K_d$ of the rabbit platelets were $6.4{\pm}1.2$pmol/mg protein and $10.9{\pm}2.1$nM and those in the [$^3H$]PAT binding were $8.6{\pm}1.1$pmol/mg protein and $1.6{\pm}0.3$nM, respectively. AP slightly increased $B_{max}$ of [$^3H$]IMI binding and both [$^3H$]IMI binding and [$^3H$]PAT binding $K_d$, and i contrast, it slightly decreased $B_{max}$ of [$^3H$]PAT binding. FO Slightly increased $K_d$ of both and [$^3H$]IMI and [$^3H$]PAT binding and slightly decreased $B_{max}$ of [$^3H$]IMI and [$^3H$]PAT binding. SA produced the significant increase of [$^3H$]PAT binding $B_{max}$ and the slight increase of both [$^3H$]IMI and [$^3H$]PAT binding $K_d$ and in contrast, it slightly decreased $B_{max}$ and of [$^3H$]IMI binding. And, the $V_{max}$ and $K_m$ of platelet [$^3H$]5-HT uptake were $24.2{\pm}2.4$pmol/$10^8$ platelets/min and $3.3{\pm}0.3$nM, respectively. The $V_{max}$ was little affected by AP, FO, or SA, but the [$^3H$]5-HT uptake $K_m$ value was moderately increased by FO. However, the platelet 5-HT content was moderately decreased by all of the 5-HT uptake inhibitors used in this study. These results seem to be consistent with the allosterical and competitive interaction of 5-HT uptake inhibiting antidepressants with each other as well as 5-HT in the 5-HT transporter binding, and provide no support for the view that the potencies of 5-HT uptake inhibitors to inhibit the [$^3H$]IMI or [$^3H$]PAT binding with 5-HT transporter complex correlate with their antidepressant potencies.