• Title/Summary/Keyword: tetrodotoxin

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EFFECT OF EUGENOL AND CAPSAICIN ON THE VOLTAGE-DEPENDENT ION CHANNELS OF TRIGEMINAL AFFERENTS (삼차신경 일차구심 뉴런의 전압의존성 이온통로에 대한 capsaicin과 eugenol의 작용)

  • Kim, Ju-Youn;Park, Sang-Jin;Choi, Gi-Woon;Choi, Ho-Young
    • Restorative Dentistry and Endodontics
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    • v.25 no.3
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    • pp.407-420
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    • 2000
  • 삼차신경절의 뉴런이 구강악안면영역에서의 촉각, 입각, 온도각 및 통각 등 다양한 감각을 중추신경계로 전달하는 역할을 하는 것은 주지의 사실이다. 이러한 신경전달에 있어서 이온통로는 감각정보를 전달하는데 핵심적인 역할을 수행하며 특히 소디움 통로는 활동전위의 발생에 중요하다. 소디움 통로는 tetrodotoxin-sensitive(TTX-s) 및 tetrodotoxin-resistant(TTX-r) 통로로 나누어지는 데 이 중 TTX-r 통로에 발생되는 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)는 capsaicin에 민감한 일차구심신경세포에서 유해자극에 의해 통각신호를 발생시키고 전달하는데 중요하다. 또한 칼슘 통로는 시냅스 전도에 있어서 필수적인 역할을 수행하고 있다 한편 치과영역에서 치수의 진정 목적으로 eugenol이 흔히 사용되고 있다. 그러나 eugenol의 그 작용 기전에 대해서 현재까지 이온 통로에 대한 상세한 결과가 없는 실정이며 최근의 보고에 의하면 eugenol이 capsaicin 수용기를 통하여 감각신경에 대한 억제작용을 나타낸다고 한다. 따라서 본 실험은 eugenol과 capsaicin이 흰쥐의 삼차신경절의 TTX-r $I_{Na}$와 칼슘통로에 어떠한 영향을 미치는지를 알아보고 eugenol이 capsaicin 수용기를 통하여 작용하는지를 검증하고자 시행되었다. 삼차신경절 뉴런은 100~150g의 흰쥐의 삼차신경절로부터 외과적으로 절제하여 통법의 화학적 및 기계적 처리를 통해 단일세포로 분리하였고 이를 whole-cell patch clamp 방법을 이용하여 시행한 바 다음과 같은 결론을 얻었다. 1. 1mM의 dugenol은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 2. $1{\mu}m$의 capsaicin은 흰쥐 삼차신경절 뉴런의 TTX-r $I_{Na}$와 HVA $I_{Ca}$를 억제하였다. 3. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하였다. 4. Capsazepine은 capsaicin의 HVA $I_{Ca}$에 대한 억제작용을 차단하지 못하였다. 결론적으로 eugenol과 capsaicin은 tetrodotoxin-resistant sodium current(TTX-r $I_{Na}$)와 high voltage-activated calcium current(HVA $I_{Ca}$)를 모두 억제하는 것으로 나타났으며, 이러한 작용이 통각의 발생과 시냅스 전달과정을 차단하여 치수 진정 목적으로 많이 사용하는 eugenol의 작용기전으로 판단된다. 한편 capsaicin의 길항제인 capsazepine을 전처치하였을 때에도 eugenol의 HVA $I_{Ca}$에 대한 억제효과는 변화가 없었다. 이와같은 결과로 보아 HVA $I_{Ca}$에 관한 한 eugenol은 capsaicin 수용기를 통하여 나타나지 않는 것으로 사료된다.

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Analysis for cancer-related studies using Puffer fish poison (복어독의 종양 관련 기존연구 논문에 대한 분석)

  • Cho, Yong Rae;Lee, Sung Bae;Park, Samuel Young;Son, Chang Gue
    • Journal of Haehwa Medicine
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    • v.28 no.2
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    • pp.1-11
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    • 2019
  • Objective: The aim of this study is to analyze the previously published research articles related to puffer fish toxin focusing on tumor. Method: Literatures were searched in PubMed database, published since 2000, using the keyword; Puffer fish, Fugu and tetrodotoxin (TTX) with cancer or tumor. Research papers were classified by year, country, study model, used material, kind of tumor and study subject. Finally, a total of 41 studies were analyzed in this study. Results: From 2000 to 2018, the most abundant papers were published in 2009 (6 studies) and almost half of the papers were studied in United Kingdom (20 studies). The 39 studies used TTX purified from puffer fish while 2 studies used crude extract of skin and gonad of puffer fish. The most used target cell line was prostate cancer (15 studies), and the next was breast cancer (14 studies). The study methods were classified into 4 clinical studies, 2 animal studies and 35 cell-based studies. Conclusions: Our results show that the overview of cancer-related studies using puffer fish poison. This information would be helpful for the puffer fish-derived drug researches in the future.

Assessment of Neuronal Cell-Based Cytotoxicity of Neurotoxins from an Estuarine Nemertean in the Han River Estuary

  • Kwon, Yeo Seon;Min, Seul Ki;Yeon, Seung Ju;Hwang, Jin ha;Hong, Jae-Sang;Shin, Hwa Sung
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.725-730
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    • 2017
  • A heteronemertean, Yininemertes pratensis, was collected in Han River Estuary, South Korea. This estuarine nemertean has been known by the local fishermen for harmful effects to the glass eels, juveniles of Japanese eel Anguilla japonica, migrating to fresh water. The present study confirmed the neurotoxic effects of this heteronemertean ribbon worm at the cellular level. Derivative types of neurotoxic tetrodotoxin (TTX), 5,11-dideoxy TTX (m/z 288) and 11-norTTX-6(S)-01 (m/z 305.97), were identified through HPLC and MALDI-TOF MS. However, significant neurotoxicity was confirmed in the fraction containing an undefined molecule corresponding to the 291.1 (m/z) peak, when tested in rat primary astrocytes and dorsal ganglion cells. This study is the first to report neurotoxins of the estuarine nemertean, fairly abundant in the Han River estuary, and suggests the long-term monitoring of population dynamics and surveillance of the toxicity in this river estuary.

Glutamate-Induced Serotonin Depletion in Fetal Rat Brainstem Cultures (흰쥐태 뇌간의 배양에서 Glutamate에 의한 Serotonin의 고갈)

  • Park, Sang-Wook;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.189-193
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    • 1993
  • Exposure of dissociated cultures from fetal rat brainstem to glutamate for upto 6 h decreased cellular contents of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in a concentration- and time-dependent manner. In addition, glutamate induced lactate dehydrogenase leakage. Tetrodotoxin did not block the effects induced by glutamate. MK-801 $(1{\mu}M)$, an N-methyl-D-aspartate (NMDA) channel blocker, but not 6-cyano-2,3-dihydroxy-7-nitro-quinoxazoline $(CNQX;\;3{\mu}M)$, a non-NMDA receptor antagonist, blocked glutamate-induced effects, indicating that these glutamate-induced responses are mediated through NMDA receptors.

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Muscle Intoxication of 'Gukmeri-bok' Puffer (Takifugu vermicularis radiatus) by Freezing and Thawing (냉동과 해동에 따른 국매리복 근육의 독화)

  • JEON Joon-Kyun;HONG Kyung-Pyo
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.37 no.3
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    • pp.175-178
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    • 2004
  • We here report that the muscle of 'gukmeri-bok' puffer fish (Takifugu vermicularis radiatus) is intoxicated after freezing and thawing processes even though it is not toxic when it is fresh. This study was carried out to investigate the effect of different freezing and thawing conditions as well as the effect of the presence of skin or viscera on the intoxication of muscle of 'gukmeri-bok' puffer during freezing and thawing process. As a result of this investigation, thawing condition, but not freezing conditions or periods played an important role in muscle intoxication. Tetrodotoxin secretory grands exist in the skin of toxic puffer fish, the skin was more responsible for the muscles intoxication than the viscera during the freezing-thawing process. In other words, no toxicity was measured in the muscle of skinned-frozen specimens even when thawed. According to this result, it is recommended that the skin and viscera must be removed before being frozen for edible purpose. Otherwise, when a whole fish should be frozen, alternative half-thawing and removal of skin from frozen specimens is recommended.

An Action Mechanism of Substance P on the Tracheal Smooth Muscle Contraction in Rabbits (토끼 기관의 평활근 수축에 미치는 substance P 의 작용기전)

  • 명창률
    • Journal of Chest Surgery
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    • v.27 no.1
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    • pp.9-14
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    • 1994
  • Substance P[SP] has been known to be a peptide which may be plays a role as a neurotransmitter in central nervous system as well as peripheral autonomic nervous system. It has been reported that SP was widely distributed in the nerve of the tracheal smooth muscle and induced the muscle contraction. However, definite action mechanism of SP in the tracheal smooth muscle was not clear, yet. Thus, present experiment was performed to elucidate an effect of substance P and an action mechanism on contraction of the smooth muscle in rabbits. In order to find a neural mechanism to the effect of SP on the tracheal smooth muscle contraction, atropine sulfate, tetrodotoxin, propranol and phentolamine were administered at 10 min before the addition of SP. Otherwise,to find effect of SP antagonists on the action of SP, [D-Pro2, D-Try7,9]SP, [D-Arg1, D-Pro2, D-Trp7,9, Leu11]SP and [D-Pro4, D-Trp7,9]SP were administered as a same fashion. These following results were obtained. 1] SP induced contraction of the tracheal smooth muscle under resting condition and the contraction was increased dose-dependently. 2] Cholinergic blocker[atropine], neural blocker[tetrodotoxin] and adrenergic blocker[propranol and phentolamine] didn`t have an effect on the contractile response. 3] Three SP antagonists inhibited the contractile response. 4] Isoproterenol relaxed the contraction induced by SP. The above results suggested that SP induced contraction of the tracheal smooth muscle directly act to the smooth muscle in rabbits. The autonomic nervous system did not seem to participate in the SP action.

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Effect of Intrahypothalamically Injected Tetrodotoxin on Pressor Responses to Electrical Stimulation in tao Hypothalamus (시상하부내로 투여한 Tetrodotoxin이 혈압 및 시상하부의 전기자극에 의한 승압반응에 미치는 영향)

  • Kim, Jong-Shik;Shin, Hong-Kee;Kim, Kee-Soon
    • The Korean Journal of Physiology
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    • v.11 no.2
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    • pp.23-31
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    • 1977
  • It is Proposed in the Present study to investigate the effects of TTX intravenously or intrahypothalamically administered on the arterial blood pressure and respiration and also to explorc effect of intrahypothalamically administered TTX on the pressor responses to electrical stimulation in the hypothalamus. The results obtained are as follows; 1) The pressor responses to electrical stimulation in the hypothalamus were markedly reduced after administration of TTX. In the $0.01\;{\mu}g/kg$ of TTX administered group, the pressor responses were almost abolished in 6 minutes and there was no tendency toward recovery throughout the experiment. 2) In $0.01\;{\mu}g/kg$ of TTX administered group, the mean arterial blood pressure and heart rate-were gradually reduced while there was a transient increase in respiratory rate followed by slow recovery thereafter. On the other hand no changes in arterial blood pressure, heart rate an4 respiration were observed in $0.005\;{\mu}g/kg$ TTX administered group. 3) Following intravenous administration of $1\;{\mu}g/kg$ TTX, the arterial blood pressure and heart rate were slowly reduced by 60 minutes while no marked changes were found in respiration. From the results of present study it is strongly suggested that TTX exerts its depressant effect not only on peripheral nerves but also on central nervous system.

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Localization of adrenergic receptors in bovine esophageal groove (소(牛) 식도구 평활근의 Adrenergic receptor 존재부위에 관한 연구)

  • Kang, Tong-mook;Cho, Je-yoel;Park, Jun-hong;Yang, Il-suk
    • Korean Journal of Veterinary Research
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    • v.33 no.4
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    • pp.617-622
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    • 1993
  • The preliminary studies on the localization of adrenoceptors were performed on smooth muscle strips of bovine esophageal groove. The mechanical activity of the muscle strip was recorded isometrically in vitro.w In the bottom circular muscle strips. the excitatory ${\alpha}-adrenergic$ responses were not blocked by tetrodotoxin$(2.1{\times}10^{-6}M)$ and denervation which was carried by cold storage of strips for 48 hrs in Tyrode's solution at $5-6{^{\circ}C}$ without oxygen supply. These excitatory ${\alpha}-adrenergic$ responses were partially blocked by atropine. In the lip longitudinal muscle strips, the inhibitory${\beta}-adrenergic$ responses were not blocked by pretreatment of tetrodotoxin and atropine. The results suggest that ${\beta}-adrenergic$ receptors mediating relaxations are located on the postsynaptic smooth muscle cells, whereas ${\beta}-adrenergic$ receptors mediating contractions are located both in the smooth muscle cells and in the cholinergic neurones.

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Toxicity of the Imported Pufferfish, Fugu flavidus ('Samchaebog'), from China (중국으로부터 수입된 삼채복(Fugu flavidus)의 독성)

  • KIM Dong-Soo;KIM Sang-Rok;LEE Myung-Ja;SEOL Myung-Hoon;JEONG Dong-Youn;KIM Hyun-Dae
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.28 no.5
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    • pp.533-538
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    • 1995
  • Ten specimens of the imported pufferfish, fugu flavidus ('Sarnchaebog'), from China were assayed for anatomical distribution of toxicity, Also, a toxic ovary of each specimen was excised, and transferred into Bio-gel P-2 column chromatography for purification of the toxins. The average toxicity of all specimens assayed was calculated to be $4.1\pm 0.5\;in\;liver,\;2.8\pm1.1\;intestine,\;0.8\pm0.5\;skin,\;2.3\pm1.5\;testis\;39.0\pm16.0\;ovary\;and\;7.0\pm2.0 MU/g$ bile, respectively; Ovary was weakly toxic, but others were non-toxic or weakly toxic. Moreover, instrumental analyses including thin layer chromatography(TLC) and electrophoresis disclosed tetrodotoxin (TTX) and anhydro tetrodotoxin (anh-TTX), respectively. The toxins of the ovary gave four peaks in high performance liquid chromatography (HPLC) whose retention times (14 and 24 min) were close to those of TTX and anh-TTX, respectively.

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Application of HPLC with Electrochemical Detection to Assaying Tyrosine Hydroxylase Activity and Dopamine Content in Dissociated Cultures of Fetal Rat Brainstem (흰쥐 태 뇌간의 세포배양에서 HPLC-전기화학검출을 이용한 Tyrosine Hydroxylase 활성 및 Dopamine의 정량)

  • Song, Dong-Keun;Wie, Myung-Bok;Park, Chan-Woong;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.27 no.1
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    • pp.7-12
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    • 1991
  • We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.

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