• Archives of Pharmacal Research
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• 제15권2호
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• pp.134-137
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• 1992

The effect of papaverine on the contractions induced by adrenergic neurotransmission in the isolated mouse vas deferens was investigated. Papaverine, $10^{-7}-10^{-5}$M, showed a dose-dependent and reversible inhibition on the induced contractions. When the frequency of stimulation was varied (2.5-20.0 Hz), the inhibitory effect tended to be marked at the lower frequencies.

• The Korean Journal of Physiology and Pharmacology
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• 제25권6호
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• pp.525-532
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• 2021

We have investigated the relative roles of α₁-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In separate experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α_1A-adrenoceptor antagonist RS100329 (10^-9M-10^-7M) significantly reduced the response to the first pulse, the α_1D-adrenoceptor antagonist BMY7378 (10^-7M-10^-6M) significantly reduced the response to the first two pulses, and the non-selective α₁-adrenoceptor antagonist prazosin (10^-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α_1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α_1D-adrenoceptor and a larger early α_1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α₁-adrenoceptor component is revealed by prazosin to be α_1B-adrenoceptor mediated. α_1B-Adrenoceptor activation probably facilitates contractions mediated by other α₁-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α₁-adrenoceptor blockade, particularly α_1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

• Journal of Ginseng Research
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• 제17권2호
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• pp.109-113
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• 1993

The effects of ginseng total saponins (GTS) on the action of U-50,488H, a $textsc{k}$-opioid receptor agonist, on the electrically induced twitch responses of mouse vats deferens were studied. U-50,488H ($10^9$~$10^{-5}$M) inhibited the twitch contractions in a dose-dependent manner, which were caused by adenosine 5'-triphosphate (ATP) released from the stimulated sympathetic nerve, and this effect was antagonized by naloxone ($10^6$ M). GTS, which itself induced the inhibition of the twitch contractions, acted additively to U-50,488H, GTS and U-50,488H had no effect on the tension of the unstimulated organs. The contractions elicited by ATP were not affected by U-50,488H, but inhibited by GTS. These results suggest that U-50,488H suppressed the twitch contractions by the inhibition of neurotransmitter release from presynaptic nerve terminals via action on opioid receptor, but G75, by inhibiting the action of the neurotransmitter on the smooth muscle.

• 한국동물생명공학회지
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• 제34권3호
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• pp.197-204
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• 2019

This study was investigated to test whether the zygote recognized the topoisomerase II beta (TOP2B) mediated DNA fragmentation in epididymal spermatozoa or the nuclease degradation in vas deferens spermatozoa by testing for the presence of gammaH2AX (γH2AX). The γH2AX is phosphorylation of histone protein H2AX on serine 139 occurs at sites flanking DNA double-stranded breaks (DSBs). The presence of γH2AX in the pronuclei of mouse zygotes which were injected with DNA broke epididymal spermatozoa was tested by immunohistochemistry at 5 and 9 h post fertilization, respectively. Paternal pronuclei that arose from epididymal spermatozoa treated with divalent cations did not stain for γH2AX at 5 h. On the other hand, in embryos injected with vas deferences spermatozoa that had been treated with divalent cations, γH2AX was only present in paternal pronuclei, and not the maternal pronuclei at 5 h. Interestingly, both pronuclei stained positively for γH2AX for all treatments and controls at 9 h after sperm injection. In conclusion, the embryos recognize DNA that is damaged by nuclease, but not by TOP2B because H2AX in phosphorylated in paternal pronuclei resulting from spermatozoa treated with fragmented DNA from vas deferens spermatozoa treated with divalent cations, but not from epididymal spermatozoa treated the same way.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1992년도 제1회 신약개발 연구발표회 초록집
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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.

• Archives of Pharmacal Research
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• 제28권9호
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2005년도 추계학술대회
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• pp.49-66
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• 2005

Panax ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized Morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. GTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, we hypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum ($\mu$-receptors) and mouse vas deferens($\delta$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H ($\kappa$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS Prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced cAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2005년도 창립30주년기념 추계 학술대회 및 정기총회
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• pp.41-63
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• 2005

Ginseng has been useful for the treatment of diverse disease in oriental countries for thousands of years. In addition, a folk medicine prescribed by seven herbal drugs including Panax ginseng has been antinarcotics in the treatment of morphine-dependent patients. Many articles have been reported on these works. Therefore, we review the protective effects of Panax ginseng on the neurotoxicity induced by abuse drugs. Ginseng total saponins (GTS) extracted and isolated by Panax ginseng antagonized morphine-induced analgesia, and inhibited the development of analgesic tolerance to and physical dependence on morphine. CTS inhibited morphine-6 dehydrogenase, which catalyzes production of mophinone from morphine, and increased hepatic glutathione level responsible to toxicity. Therefore, wehypothesized that these dual actions of ginseng can be associated with the detoxication of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contraction in guinea pig ileum (${\mu}$-receptors) and mouse vas deferens(${\delta}$-receptors) were not mediated through opioid receptors, suggesting non-opioid mechanisms. On the hand, antagonism of U-50,488H (${\kappa}$-agonist)-induced antinociception is mediated by serotonergic mechanisms. GTS also inhibited hyperactivity, reverse tolerance (sensitization) and conditioned place preference-induced by psychostimulants such as methamphetamine, cocaine and morphine. On the other hand, GTS reduced the dopamine levels induced by methamphetamine. Moreover, GTS blocked the development of dopamine receptor activation, showing antidopaminergic effect. We suggest that GTS prevent the methamphetamine-induced striatal dopaminergic neurotoxicity. In addition, Ginsenoside also attenuates morphine-induced CAMP signaling pathway. These results suggested that GTS might be useful for the therapy of the adverse actions of drugs with abuse liability.