• Korean Journal of Veterinary Research
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• v.38 no.3
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• pp.525-534
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• 1998

신장 근위세뇨관세포들은 사구체에서 여과된 물질의 재흡수, 분비 및 대사에 관여하는 여러 호르몬들의 수용체들을 가지고 있다. 이들중에서 norepinephrine(NE)과 angiotensin II(ANG II)는 $Na^{+}/H^+$ 상호운반계를 조절함으로써 혈압조절에 관여하는 것으로 알려져 있으나 이들의 상호관계에 대해선 연구보고가 많지 않다. 본 연구는 초대배양한 토끼신장 근위세뇨관세포를 이용한 $Na^+$ uptake 실험을 통하여 NE이 어떠한 수용체를 통하여 $Na^{+}/H^+$ 상호운반계를 조절하는지 그리고 이러한 작용에 있어서 NE과 ANG II의 상호관계를 알아보고자 실시하였다. NE(>$10^{-9}M$)은 $Na^+$ uptake를 유의성 있게 증가시켰다($10^{-9}M$ NE : $27{\pm}4%$ increase vs. Control;p < 0.05). $\alpha$ 길항제(phentolamine, $10^{-10}M$)는 NE($10^{-9}M$)에 의해 유도된 $Na^+$ uptake를 유의성 있게 차단하였으나 (phentolamine+NE : $29{\pm}5%$ inhibition vs. NE ; p〈 0.05), ${\alpha}_1$ (pra-zosin, $10^{-10}M$) 및 ${\alpha}_2$ 길항제(yohimbine, $10^{-10}M$)는 부분적으로 차단하였다. ${\beta}$ 길항제(propra-nolol, $10^{-10}M$)도 역시 NE에 의해 유도된 $Na^+$ uptake를 유의성 있게 차단하였으나(propranolol+NE : $24{\pm}6%$ inhibition vs. NE ; p< 0.05), ${\beta}_1$(atenolol, $10^{-10}M$) 및 ${\beta}_2$ 길항제(butoxamine, $10^{-10}M$)는 부분적으로 차단하였다. 이러한 결과들은 NE에 의해 유도된 $Na^+$ uptake 증가작용은 ${\alpha}$(${\alpha}_1$ 및 ${\alpha}_2$ )와 ${\beta}$(${\beta}_1$ 및 ${\beta}_2$) 수용체 모두를 통하여 일어난다는 것을 시사해주고 있다. ANG II($10^{-11}M$) 또는 NE(${\alpha}_1$, ${\alpha}_2$, ${\beta}_1$, ${\beta}_2$ 작동제) 단독처리군의 $Na^+$ uptake는 대조군에 비해 유의성 있게 증가하였으나 (ANG II : $23{\pm}9%$ increase vs. Control; p < 0.05), 병합처리시 상승작용은 나타나지 않았다. ${\alpha}$ 또는 ${\beta}$ 길항제 처리시 NE 및 ANG II에 의해 유도되었던 $Na^+$ uptake 증가는 유의성 있게 차단되었다(phentolamine+NE+ANG II : $25{\pm}3%$ inhibition, propranolol+NE+ANG II : $24{\pm}6%$ inhibition vs. NE+ANG II, respectively ; p〈 0.05). 이 결과들은 $Na^+$ uptake에 있어서 ${\alpha}$(${\alpha}_1$ 및 ${\alpha}_2$)와 ${\beta}$(${\beta}_1$ 및 ${\beta}_2$) 수용체와 ANG II의 관련성을 시사해 준다. 결론적으로 토끼 신장 근위세뇨관세포에서 NE은 ${\alpha}_1$, ${\alpha}_2$, ${\beta}_1$ 및 ${\beta}_2$ 수용체를 통하여 $Na^+$+ uptake를 증가시켰으며 이들 수용체는 ANG II $Na^+$ uptake 증가작용에 관여하였다.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.145-152
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• 1995

The effects and interactions of $4{\beta}-phorbol$ 12,13-dibutyrate(PDB) and polymyxin B(PMB) with adenosine on the electrically-evoked norepinephrine (NE) release were studied in the rat hippocampus. Slices from the rat hippocampus were equilibrated with $^3H-noradrenaline$ and the release of the labelled product, $^3H-NE$, which evoked by electrical stimulation$(3\;Hz,\;2\;ms,\;5\;VCm^{-1},\;rectangular\;pulses)$ was measured. PDB$(0.3{\sim}10\;{\mu}M)$, a selective protein kinase C(PKC) activator, increased the evoked NE release in a dose related fashion while increasing the basal rate of release. And the effects of $1\;{\mu}M$ PDB were significantly inhibited by $0.3\;{\mu}M$ tetrodotoxin(TTX) pretreatment or $Ca^{++}-free$ medium. $PMB(0.03{\sim}1\;mg)$, a specific PKC inhibitor, decreased the NE release in a dose dependent manner while increasing the basal rate of release. Adenosine $(1{\sim}10\;{\mu}M)$ decreased the NE release without changing the basal rate of release, and this effect was significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine$(2\;{\mu}M)$, a selective $A_1-receptor$ antagonist, treatment. Also, adenosine effects were significantly inhibited by PDB-and PMB-pretreatment. These results suggest that the PKC plays a role in the NE release in the rat hippocampus and might be participated in a post-receptor mechanism of the $A_1-adenosine$ receptor.

• YAKHAK HOEJI
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• v.30 no.3
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• pp.111-120
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• 1986

The influence of debrisoquine on pressor actions of norepinephrine (NE) and tyramine (TR) was investigated in rabbits. Debrisquine(D), in the doses of 1.0, 3.0 and 6.0.mu.g/kg, i.v. potentiated significantly the pressor actions of NE and TR, except the action of TR in the dose of 1.0mg/kg of debrisoquine. NE response potentiated by debrisoquine was not affected by tranylcypromine, a MAO inhabiter, or desipramine, a NE uptake blocking agent, but augmented by reserpine, a NE depleting agent, or bethanidine, a sympathetic neuronal blocking agent. NE response potentiated by tranylcypromine or desipramine was augmented by debrisoquine, while NE response potentiated by reserine or bethanidine was not affected by debrisoquine. TR response potentiated by debrisoquine was weakened by tranylcypromine, desipramine or reserpine, and not affected by bethanidine. TR response in rabbit pretreated with tranylcypromine, desipramine or reserpine was augmented by debrisoquine, but in rabbit pretreated with bethanidine was not affected by debrisoquine.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.1-11
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• 1996

Since it has been reported that the depolarization-induced norepinephrine (NE) release is inhibited by activation of presynaptic $A_1-adenosine$ heteroreceptor in hippocampus, a large body of experimental data on the post-receptor mechanism of this process has been accumulated. But, the post-receptor mechanism of presynaptic $A_1-adenosine$ receptor on the NE release has not been clearly elucidated yet. Therefore, it was attempted to clarify the post-receptor mechanisms of the $A_1-adenosine$ receptor-mediated control of NE release in this study. Slices from rat hippocampus were equilibrated with $^3H-norepinephrine$ and the release of the labelled products was evoked by electrical stimulation (3 Hz, 5 $Vcm^{-1}$, 2 ms, rectangular pulses), and the influence of various agents on the evoked tritium-outflow was investigated. Adenosine, in concentrations ranging from $1{\sim}30{\mu}M$, decreased the NE release in a dose-dependent manner, without affecting the basal rate of release. The adenosine effects were significantly inhibited by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, $2{\mu}M$), a selective $A_1-receptor$ antagonist. The responses to N-ethylmaleimide (NEM, 10 & $30{\mu}M$), a SH-alkylating agent of G-protein, were characterized by increments of the evoked NE-release and the basal release, and the adenosine effects were completely abolished by NEM pretreatment. $4{\beta}-Phorbol$ 12,13-dibutyrate (PDB, $1{\mu}M$), a specific protein kinase C (PKC) activator, increased the evoked NE release, whereas polymyxin B sulfate (PMB,0.1 mg), a PKC inhibitor, decreased the release, and the adenosine effects were inhibited by these agents. Nifedipine $(1{\mu}M)$, a $Ca^{2+}-channel$ blocker of dihydropyridine analogue, did not affect the adenosine effect. Tetraethylammonium (TEA, 3 mM) increased the evoked NE release, and inhibited the adenosine effects, but glibenclamide, a ATP dependent $K^+-channel$ blocker, did not. Finally, 8-bromo cyclic AMP (100 & $300{\mu}M$), a membrane-permeable analogue of cAMP, did not alter the NE release, but adenosine effects were inhibited by pretreatment with 8br-cAMP. These results suggest that the decrement of the evoked NE-release by $A_1-adenosine$ receptor is mediated by the C-protein, which is coupled to protein kinase C, adenylate cyclase system and TEA sensitive $K^+-channel$, and that nifedipine-sensitive $Ca^{2+}-channel$ and glibenclamide-sensitive $K^+-channel$ are not involved in this process.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.27-35
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• 1993

Effects of the endothelium on the contractile responses to norepinephrine (NE) were investigated in isolated helical strips of the proximal and distal coronaries artery of pigs. The helical strips were immersed in Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $35^{\circ}C$ and its isometric tension was measured. NE relaxed the strips precontracted with acetylcholine from both the proximal and distal coronary artery. NE-induced relaxation, which might be induced mainly by $\beta$-adrenoceptor function was dominant in the distal coronary arteries. NE-induced relaxation was converted to a contraction after $\beta$-adrenoceptor blockade with propranolol $(3{\times}10^{-6}M)$. ${\alpha}$-adrenoceptor-mediated contraction by NE was greater in the proximal coronary artery than the distal coronary artery. Quantitatively, ${\alpha}_1$-adrenoceptor mediated contraction by NE was greater than ${\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries. NE-induced relaxation was decreased by rubbing of endothelium in both arteries. ${\alpha}_1-and\;{\alpha}_2$-adrenoceptor mediated contraction by NE were potentiated by rubbing of endothelium in both arteries. Pretreatment with methylene blue, an inhibitor of soluble guanylate cyclase, increased ${\alpha}_1-\;and\;{\alpha}_2$-adrenoceptor mediated contraction by NE in both arteries with endothelium. From the above results, we suggest that the effect of activation of $\alpha$-adrenoceptors by NE may be modulated by endothelium in the proximal and distal coronary arteries of pigs. This effect may be mediated via endothelium derived relaxing factor.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.33-41
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• 1993

Central analgesic effect of capsaicin was assessed by the tail flick reflex (TFR) test, using male Sprague-Dawley rats under anesthesia with pentobarbital sodium (induction with 40 mg/kg and maintenance with $4{\sim}8\;mg/kg/hr$). Level of norepinephrine in the spinal cord was also measured. Capsaicin, $35{\sim}150\;{\mu}g$, was injected intrathecally, and the TFR latency was measured before, 10, 30, and 60 minutes after the drug administration. TFR latency was increased 100% or more immediately by intrathecal capsaicin, from 2.9 seconds to the maximum of 7.0 seconds at 10 minute after the drug; P<0.01. The increase in TFR latency was maintained during the course of experiment of 2 hours. Concomitant reduction of NE content in the spinal cord was observed; from 16 ng/mg protein to 7 ng/mg protein. On the other hand, subcutaneous injection of capsaicin of 50 mg/kg did not change the TFR latency although the NE content reduced similarly to the case of intrathecal injection. Pretreatment of the animal with 0.5 mg/kg of MK-801 reversed the increase of TFR latency and NE reduction induced by intrathecal capsaicin. These results suggest that capsaicin causes analgesia at the spinal cord level by activating the excitatory amino acid-NE-dorsal horn interneurons axis of the descending inhibitory pain modulation pathway.

• Korean Journal of Veterinary Research
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• v.50 no.2
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• pp.79-84
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• 2010

The molecule possessing ankyrin-repeats induced by lipopolysaccharide (MAIL) protein is a novel member of the $Ikappa{\beta}$ family. In the present study, we examined the effect of norepinephrine (NE) on MAIL mRNA expression in primary cultured mouse hepatocytes and non-parenchymal liver cells. MAIL mRNA expression in hepatocytes and non-parenchymal liver cells was not directly influenced by NE. However, MAIL mRNA expression in hepatocytes was significantly induced by incubation with a culture medium of non-parenchymal liver cells, treated with NE. Pretreatment with an interleukin (IL)-1 receptor antagonist significantly attenuated the stimulatory effect of the medium. Moreover, exogenous $IL-1{\beta}$ induced MAIL mRNA expression in hepatocytes, while IL-6 and tumor necrosis factor $\alpha$ did not. The concentration of $IL-1{\beta}$ in the medium of non-parenchymal liver cells was significantly increased after NE-treatment. These results suggest that NE can induce MAIL mRNA expression in hepatocytes through $IL-1{\beta}$, released from non-parenchymal liver cells.

• Korean Journal of Acupuncture
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• v.33 no.2
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• pp.75-83
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• 2016

Objectives : A previous study demonstrated that the connecting points of three yang meridians attenuated changes of nNOS, and Norepinephrine(NE) in rats. The current study investigated the changes in nNOS, NO and NE upon the needle insertion at varying depths at the connecting point of three yin meridians of the hand. Methods : Needles were inserted into rats, on both left and right sides of the connecting point, including the LU7, HT5 and PC6 acupoints which are three yin meridians of the hand. After insertion, needles were retained for five minutes. Each acupuncture groups were treated acupuncture at each acupoint and at the depths of superficial, middle and deep layer. After the retention, blood was drawn via cardiac puncture, and tissues of each point near meridian vessel was extracted to examine the changes in the expression of nNOS, NO and NE. Results : Compared with the superficial layer group, nNOS production significantly decreased in the middle and deep layer at LU7 acupoint group and in the deep layer at HT5, PC6 acupoint group. The tissue NE decreased in the deep layer on PC6 acupoint and the plasma NE increased at the middle layer at LU7 acupoint group but decreased at the deep layer on at LU7 acupoint group. Conclusions : Acupuncture at connecting points of three yin meridians of the hand can regulate the activities of nNOS, and NE.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.2
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• pp.87-91
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• 2002

The aim of this study was to investigate the role of $Ca^{2+}-channel$ blockers in norepinephrine (NE) release from rat hippocampus. Slices and synaptosomes were incubated with $[^3H]-NE$ and the releases of the labelled products were evoked by 25 mM KCl stimulation. Nifedipine, diltiazem, nicardipine, flunarizine and pimozide did not affect the evoked and basal release of NE in the slice. But, diltiazem, nicardipine and flunarizine decreased the evoked NE release with a dose-related manner without any change of the basal release from synaptosomes. Also, a large dose of pimozide produced modest decrement of NE release. ${\omega}-conotoxin$ (CTx) GVIA decreased the evoked NE release in a dose-dependent manner without changing the basal release. And ${\omega}-CTxMVIIC$ decreased the evoked NE release in the synaoptosomes without any effect in the slice, but the effect of decrement was far less than that of ${\omega}-CTxGVIA.$ In interaction experiments with ${\omega}-CTxGVIA,\;{\omega}-CTxMVIIC$ slightly potentiated the effect of ${\omega}-CTxGVIA$ on NE release in the slice and synaptosomal preparations. These results suggest that the NE release in the rat hippocampus is mediated mainly by N-type $Ca^{2+}-channels,$ and that other types such as L-, T- and/or P/Q-type $Ca^{2+}-channels$ could also be participate in this process.

• The Korean Journal of Emergency Medical Services
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• v.23 no.3
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• pp.165-173
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• 2019

Purpose: Norepinephrine (NE) is a neurotransmitter of the sympathetic nervous system. It is used for treating hypotension on distributive shock, central nervous system injury, or sepsis. There are several reports that state that alcohol suppresses vasoconstriction by NE. Thus, our hypothesis is that the effect of NE is reduced in alcohol-drinking patients with distributive shock. We investigated whether alcohol suppresses NE-induced contraction and aimed at finding a solution to this problem. Methods: For this study, we used the aorta from male Sprague-Dawley rats (9-11 weeks) and an isometric contraction system. Results: Our results showed that alcohol suppresses NE contraction and does not affect epinephrine induced a contraction. Moreover, in the presence of alcohol, a 7:3 mixture of NE and epinephrine induced a contractile force similar to that induced by NE under normal conditions. Conclusion: We found that the vasoconstrictive force of NE decreased in the blood vessels in which alcohol was present, which was not because endothelial cells. The reduced contractile force was most similar to that induced by a 7:3 mixture of NE and epinephrine.