• 대한수의학회지
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• 제38권3호
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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.

• 대한약리학회지
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• 제31권2호
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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.

• 약학회지
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• 제30권3호
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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.

• 대한약리학회지
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• 제32권1호
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• pp.1-11
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• 1996

흰쥐 해마(hippocampus)에서 norepinephrine(NE) 유리에 미치는 $A_1-adenosine$ 수용체의 post-receptor 기전에 관한 지견을 얻고자 하여 $^3H-norepinephrine$으로 평형시킨 해마 절편을 사용하여 adenosine의 $^3H-NE$ 유리에 미치는 여러가지 약물의 영향을 관찰하였다. Adenosine($1{\sim}30{\mu}M$)은 전기자극(3 Hz, 2 ms, 5 Vcm-1, 구형파)에 의한 NE 유리를 용량 의존적으로 감소시켰고, 이 효과는 선택적인 $A_1-adenosine$ 수용체 차단제인 $8-cyclopentyl-1,3-dipropylxanthine(2{\mu}M)$에 의해 차단되었다. G-단백 억제제인 N-ethylmaleimide(NEM, 10과 $30{\mu}M$)는 그 자체로써 전기자극으로 유발시킨 NE 유리를 증가시켰으며, adenosine의 NE 유리 억제효과는 NEM 전처리에 의하여 완전히 소실되었다. Protein kinase C 활성화제인 $4{\beta}-phorbol$ 12,13-dibutyrate(PDB, $1{\mu}M$)는 NE 유리 증가를 일으켰고, 이 효소 억제제인 $4{\beta}-polymyxin$ B(PMB, 0.1 mg)는 NE 유리감소를 일으켰으며, adenosine에 의한 NE 유리 감소효과는 PDB에 의해 억제되었고, PMB 전처리하에서는 감소효과가 출현하지 않았다. $Ca^{2+}$-통로 차단제인 $nifedipine(1{\mu}M$)은 adenosine의 NE 유리 억제효과에 영향을 미치지 못하고, ATP에 의존적인 $K^+-$통로 차단제인 glibenclamide역시 adenosine의 NE 유리 억제효과에 영향을 미치지 못하였다. 그러나 delayed rectifier $K^+-$통로 차단제인 tetraethylammonium(TEA, 3 mM)은 그 자체로 NE 유리를 증가 시켰으며, adenosine의 NE 유리 억제효과를 차단함을 볼 수 있었다. 8-bromo-cAMP(100과 $300{\mu}M$) 그 자체로는 NE 유리에 별다른 영향을 미치지 못하였으나 8-bromo-cAMP 전처리에 의하여 adenosine의 NE 유리 억제효과가 억제됨을 볼 수 있었다. 이상의 실험결과로 흰쥐 해마에서 $A_1-adenosine$ 수용체를 통한 adenosine의 NE 유리 감소는 G-단백에 의존적이며, 이러한 효과에 protein kinase C, TEA에 예민한 $K^+-$통로 및 adenylate cyclase계가 복합적으로 관여하고 nifedipine에 예민한 $Ca^{2+}-$통로와 glibenclamide에 예민한 $K^+-$통로는 관여하지 않는 것으로 사료된다.

• The Korean Journal of Physiology
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• 제27권1호
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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.

• 대한약리학회지
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• 제29권1호
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• pp.33-41
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• 1993

Capsaicin의 중추신경계에 대한 진통효과를 척수 수준에서 규명하고, 이에 대한 norepinephrine (NE)계의 역할을 규명하기 위하여 tail flick reflex (TFR) latency time의 증가와 척수 내 NE 양의 변화를 측정하였다. 웅성의 Sprague-Dawley 백서를 pentobarbital sodium으로 마취를 하여 femoral vein cannulation과 intrathecal catheterization을 하였고, 이를 통하여 시험약제를 투여하였다. TFR은 capsaicin 또는 용매 투여전, 투여후 10분, 30분, 60분, 때로는 2시간에 측정하였다. MK-801은 capsaicin 투여전 20분에 femoral vein을 통하여 주입하였다. $35{\sim}150{\mu}g$의 capsaicin을 intrathecal로 주었을 때, TFR latency가 최고치인 7초를 넘어 정상인 2.9초에 비해 100% 이상의 증가를 보였고, 척수 내 NE은 16 ng/mg protein에서 7 ng/mg protein으로 50% 이상 감소하였다. 이와 같은 TFR latency의 증가와 NE의 감소는 전 실험기간 (capsaicin 투여후 2시간)에 걸쳐 관찰되었다. 반면, 50mg/kg의 capsaicin을 피하로 전신투여 하였을 경우에 척수 NE은 같은 변화를 보였으나 TFR latency의 차이는 없었다. 또한, 0.5 mg/kg의 MK-801를 i.v.로 전처치 하였을 때, intrathecal capsaicin에 의한 TFR latency의 증가와 척수 내 NE의 감소가 모두 억제되었다. 이상의 결과는 capsain이 excitatory aminoacid (EAA)계 - NE계 - 척수 dorsal horn으로 이루어진 동통전달의 하행성 억제계 축의 활성을 항진시켜 진통효과를 가져옴을 보여준다. 또한, capsaicin의 피하 주사시에 진통효과를 볼 수 없음을 말초 동통전달신경의 흥분에 의한 중추 동통전달계 환성의 촉진이 진통 효과를 상쇄함을 암시한다.

• 대한수의학회지
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• 제50권2호
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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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• 제33권2호
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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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• 제6권2호
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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.

• 한국응급구조학회지
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• 제23권3호
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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.