• Journal of Ginseng Research
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• 제35권2호
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• pp.176-190
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• 2011

There seems to be some controversy about the effect of total ginseng saponin (TGS) on the secretion of catecholamines (CA) from the adrenal gland. Therefore, the present study aimed to determine whether TGS can affect the CA release in the perfused model of the adrenal medulla isolated from spontaneously hypertensive rats (SHRs). TGS (15-150 ${\mu}g/mL$), perfused into an adrenal vein for 90 min, inhibited the CA secretory responses evoked by acetylcholine (ACh, 5.32 mM) and high $K^+$ (56 mM, a direct membrane depolarizer) in a dose- and time-dependent fashion. TGS (50 ${\mu}g/mL$) also time-dependently inhibited the CA secretion evoked by 1.1-dimethyl-4 -phenyl piperazinium iodide (DMPP; 100 ${\mu}M$, a selective neuronal nicotinic receptor agonist) and McN-A-343 (100 ${\mu}M$, a selective muscarinic M1 receptor agonist). TGS itself did not affect basal CA secretion (data not shown). Also, in the presence of TGS (50 ${\mu}g/mL$), the secretory responses of CA evoked by veratridine (a selective $Na^+$ channel activator (50 ${\mu}M$), Bay-K-8644 (an L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) were significantly reduced, respectively. Interestingly, in the simultaneous presence of TGS (50 ${\mu}g/mL$) and N${\omega}$-nitro-L-arginine methyl ester hydrochloride [an inhibitor of nitric oxide (NO) synthase, 30 ${\mu}M$], the inhibitory responses of TGS on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, cyclopiazonic acid, and veratridine were considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of TGS-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of TGS (150 ${\mu}g/mL$) was greatly elevated compared to the corresponding basal released level. Taken together, these results demonstrate that TGS inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal medulla of the SHRs. It seems that this inhibitory effect of TGS is mediated by inhibiting both the influx of $Ca^{2+}$ and Na+ into the adrenomedullary chromaffin cells and also by suppressing the release of $Ca^{2+}$ from the cytoplasmic calcium store, at least partly through the increased NO production due to the activation of nitric oxide synthase, which is relevant to neuronal nicotinic receptor blockade, without the enhancement effect on the CA release. Based on these effects, it is also thought that there are some species differences in the adrenomedullary CA secretion between the rabbit and SHR.

• 대한수의학회지
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• 제38권4호
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• pp.712-719
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• 1998

Thyroid function is mainly regulated through cAMP and phophatidylinositol, and it is well known that TSH-stimulated thyroxine ($T_4$) release is inhibited by catecholamine from mouse thyroids via the ${\alpha}_1$-adrenoceptor stimulation. Previous study has established that the inhibition of $T_4$ release by ${\alpha}_1$-adrenoceptor stimulation results in activated protein kinase C (PKC). The purpose of this study was to determine if ion transport systems are involved in the inhibition of $T_4$ release elicited by ${\alpha}_1$-adrenergic agonist in mouse thyroids. TSH-, IBMX- and cAMP analogue-stimulated $T_4$ release were significantly inhibited by methoxamine, R59022 (diacylglycerol kinase inhibitor), and MDL (adenylate cyclase inhibitor). TSH-stimulated $T_4$ release could be inhibited by Bay K 8644 and cyclopiazoic acid, but not by verapamil and tetrodotoxin. The addition of nifedipine ($Ca^{2+}$ channel blocker), tetrodotoxin and lidocaine ($Na^+$ channel blockers), but not amiloride (EIPA) and ryanodine, completely blocked the inhibitory effects of methoxamine on $T_4$ release. TSH-stimulated $T_4$ release was also inhibited by benzamil ($Na^+-Ca^{2+}$ exchange inhibitor). TSH-, IBMX- and cAMP-stimulated $T_4$ release were inhibited by methoxamine or R59022, these effects were reversed by nifedipine. but not by verapamil. Furthermore, nifedipine reversed the inhibitory effects of benzamil and R59022 on TSH-stimulated $T_4$ release. These data suggest that the observed ${\alpha}_1$-adrenoceptor-mediated inhibition of $T_4$ release in mouse thyroids is the result of an increase in intracellular $Na^+$ or $Ca^{2+}$ effected via activation of fast $Na^+$ or nifedipine-sensitive $Ca^{2+}$ channels, and that $Na^+-Ca^{2+}$ exchange may play an important role in reducing thyroid hormone by increasing intracellular $Ca^{2+}$.

• 대한약리학회지
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• 제23권2호
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• pp.57-75
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• 1987

Two modalities of gonadotropin secretion, pulsatile gonadotropin and preovulatory gonadotropin surge, have been identified in the mammals. Pulsatile gonadotropin secretion is modulated by the pulsatile pattern of GnRH release and complex ovarian steroid feedback actions. The neural mechansim that regulates the pulsatile release of GnRH in the hypothalamus is called "GnRH pulse generator". Ovarian steroids, estradiol and progesterone, appear to exert thier feedback effects both directly on the pituitary to modulate gonadotropin release and on a hypothalamic site to modulate GnRH release; estradiol primarily affects the amplitude while progesterone decreases the frequency of the pulsatile GnRH. Steroid hormones are known to affect catecholamine transmission in brain. MBH-POA is richly innervated by NE systems and close apposition of NE terminals and GnRH cell bodies occurs in the MBH as well as in the POA. NE normally facilitates pulsatile LH release by acting through ${\alpha}-receptor$ mechanism. However, precise nature of facilitative role of NE transmission in maintaining pulsatile LH has not been clearly understood. Close apposition of DA and GnRH terminals in ME might permit DA to influence GnRH release. Action of DA transmission probably is mediated by axo-axonic contacts between GnRH and DA fibers in the ME. Dopamine transmission does not normally regulate pulsatile LH release, but under certain conditions, increased DA transmission inhibit LH pulse. Endogenous opioid acts to suppress the secretion of GnRH into hypophysial portal circulation, thereby inhibiting gonadotropin secretion. However, an interaction between endogenenous opioid peptides and gonadotropin release is a complex one which involves ovarian hormones as well. LH secretion appears to be most suppressed by endogenenous opioids during the luteal phase, at a time of elevated progesterone secretion. The arcuate nucleus contains not only cell bodies for GnRH and ${\beta}-endorphin$ but also a dense aborization of fibers suggesting that GnRH release is changed by the interactions between GnRH and ${\beta}-endorphin$ cell bodies within the arcuate nucleus. The frequency and amplitude of pulsatile LH release seem to be increased during the preovulatory gonadotropin surge. Estradiol exerts positive feedback action on the hypothalamo-pituitary axis to trigger preovulatory LH surge. GnRH is also crucial hormonal stimulus for preovulatory LH surge. It is unlikely, however, that increased secretion of GnRH during the preovulatory gonadotropin surge represents an obligatory neural signal for generation of the LH discharge in primates including human. Modulation of preovulatory LH surge by catecholamines has been studied almost exclusively in rats. NE and E may be involved in distinct way to accumulate GnRH in the MBH and its release into the hypophysial portal system during the critical period for LH surge on proestrus in rats. However, the mechanisms whereby augmented adrenergic transmission may facilitate the formation and accumulation of GnRH in the ME-ARC nerve terminals before the LH surge have not been clearly understood.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.147-147
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• 1998

The present study was designed to examine the effect of total ginseng saponin on CA secretion evoked by activation of nicotinic receptors from the isolated perfused rat adrenal glands. Total ginseng saponin given (100 $\mu\textrm{g}$/20 min) into an adrenal vein did fail to produce alteration of spontaneous CA release from the rat adrenal medulla. Acetylcholine (5.32 mM)- and DMPP (100 uM, a selective ncotinic receptor agonist)-evoked CA secretory responses were reduced markedly by the pretreatment with the total ginseng saponin at a rate of 100 $\mu\textrm{g}$/6.2 $m\ell$/20 min, respectively.

• 약학회지
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• 제25권1호
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• pp.15-25
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• 1981

This study was attempted to investigate the action of debrisoquine, a sympathetic blocking agent presently employed in treating hypertension, on renal function and to elucidate the mechanism of its action. Debrisoquine, given intravenously, elicited increased urine flow, osmolar and free water clearances, along with marked increases in excretion of both sodium and potassium. Glomerular filtration rate also increased, but renal plasma flow tended to decrease, so that the filtration fraction tended to increase. Rates of reabsorption of sodium and potassium in renal tubules were also significantly diminished. The diuresis induced by debrisoquine was completely blocked by treatment with phentolamine and reserpine, and also markedly inhibited by acute renal denervation. Debrisoquine, when injected directly into a renal artery, produced antidiuretic effect and a reduction in urinary excretion of sodium and potassium, along with diminished renal plasma flow and increased filtration fraction. The above observations indicate that debrisoquine, when given intravenously, induces diuresis in the dog as a result of both diminished tubular reabsorption of electrolytes and of renal hemodynamic changes, which seem to be related to its inhibitory action of catecholamine-release from the sympathetic nerve endings.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.401-415
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• 2002

Lim and his coworkers (1987; 1988; 1989) have also found that all of total Ginseng saponin, panaxadiol-and panaxatriol-type saponins cause the increased secretion of catecholamines (CA) in a $Ca^{2+}$ -dependent fashion from the isolated perfused rabbit adrenal glands through the activation of cholinergic (both nicotinic and muscarinic) receptors. These CA secretory effects are partly due to the direct action on the rabbit adrenomedullary chromaffin cells. However, the present study was designed to examine the effect of total ginseng saponin on CA secretion evoked by activation of cholinergic nicotinic receptors in the isolated perfused model of the rat adrenal gland. Total ginseng saponin given (100 ${\mu}g$/20 min) into an adrenal vein did fail to produce alteration of spontaneous CA release from the rat adrenal medulla. Acetylcholine(5.32 mM)- and DMPP(100 ${\mu}M$, a selective nicotinic receptor agonist)-evoked CA secretory responses were reduced markedly after the pretreatment with the total ginseng saponin at a rate of 100 ${\mu}g$/6.2 ml/20 min, respectively. Pretreatment with total ginseng saponin also depressed greatly high potassium (56 mM, a membrane depolarizing agent)- and Bay-K-8644 (10 ${\mu}M$, a calcium channel activator)-induced CA secretions. Taken together, it is thought that total ginseng saponin can inhibit the releasing effect of CA evoked by nicotinic receptor stimulation from the isolated perfused rat adrenal medulla, which seems to be associated to the direct inhibition of influx through L-type calcium channel into the rat adrenomedullary chromaffin cells. It seems that there is species differences in the adrenomedullary catecholamine secretion between the rabbit and rat.

• 대한약리학회지
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• 제32권3호
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• pp.357-371
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• 1996

리튬(Lithium)은 임상에서 조울병 치료에 이용되고 있다. 본 연구는 흰쥐 적출 관류부신 으로부터 catecholamine (CA) 분비에 대한 리튬의 작용을 검색 하고 그 기전을 규명하고자 하여 얻어진 결과는 다음과 같다. 정상 Krebs-bicarbonate 용액내의 $Na^+$ (118.4 mM)을 리튬으로 대치하여 관류하였을때 CA 분비는 점차적인 증가를 나타내었으며, $30{\sim}60$분에서 최대 분비작용을 나타내었다. Li-Krebs액은 모든 실험에서 부신정맥을 통해서 2시간동안 관류하였다. Li-Krebs에 의한 CA 분비반응은 $Ca^{++}-free$ Krebs액으로 전처치한 상태에서 유의하게 억제되었다. 이와같은 Li-Krebs 액에 의한 CA 분비작용은 nicardipine ($10^{-6}$ M), TMB-8 ($10^{-5}$ M) 및 chlorisondamine ($10^{-6}$ M) 등을 20 분간 각각 전처치 하였을때 현저히 감약되었으나 pirenzepine ($2{\times}10^{-6}$ M)에 의해서는 별다른 영향을 받지 않았다. $Na^+$ pump 억제제인 ouabain ($10^{-4}$ M)으로 20 분간 전처치한 후 Li-Krebs에 의한 CA 유리작용은 뚜렷이 억제되었다. 더우기 tetrodotoxin ($5{\times}10^{-7}$ M)으로 20 분간 전처치 하였을때도 Li-Krebs에 의한 CA 분비반응은 현저히 감약되었다. 이상과 같은 실험결과를 종합하여 보면, 리튬은 흰쥐 부신수질의 크롬 친화성 세포내에 측적됨으로써 칼슘의존성의 CA 분비작용을 일으키며, 이러한 분비작용은 i) 크롬친화성 세포의 탈분극과 이어서 voltage-sensitive 칼슘채널의 개방과 ii) $[Li]_i-[Ca]_0$ counter-transport system의 활성화를 통한 두가지 작용기전에 의해서 매개되는 것으로 생각된다.

• 한국콘텐츠학회논문지
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• 제12권3호
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• pp.214-221
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• 2012

최근 일부 연구자에 의해 근막의 자율신경지배가 보고되고 있다. 그러나 근막이완술의 효과에 대한 신경 생리학적 설명과 근거는 없는 실정이다. 이에 본 연구의 목적은 근막이완술에 의해 자율신경계의 흥분이 변화될 수 있는지의 여부를 알아보고자 하였다. 본 연구에서는 건강한 20대 피검자 30명을 15명씩 무작위로 근막이완술군(MG)과 위약대조군(PCG)로 배치하였다. 근막이완술군으로 배정된 피검자들에게는 치료대에 바로 누운 자세에서 두개 기저부 이완기법(cranial base release)을 5분간 적용하였고 위약대조군으로 배정된 피검자들은 같은 자세와 절차를 거치지만 실제 근막이완술을 적용하지 않는 위약 치료를 적용하였다. 근육의 유연성은 경부의 관절가동범위로 측정하였으며 자율신경계의 변화는 심박수, 혈압 그리고 에피네프린과 노르에피네프린의 수치로 측정하였다. 본 연구의 결과는 다음과 같다. 1. 근막이완술군에서 신전과 측방굴곡의 가동범위 변화율이 유의하게 증가하였다. 2. 심박수와 혈압, 그리고 에피네프린의 변화율은 두 군간 유의한 차이가 없었다. 3. 노르에피네프린의 변화율은 두 군간 유의한 차이가 있었다. 본 연구의 결과 근막이완술이 자율신경계의 흥분을 변화 시킬 수 있다는 근거는 없었다.

• 대한약리학회지
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• 제27권2호
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• pp.167-181
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• 1991

Adenylate cyclase 효소를 활성화시키는 약물인 Forskolin의 흰쥐 적출관류 부신으로부터 Ach, excess $K^+$, McN-A-343 및 caffein에 의한 catecholamines (CA) 분비작용에 대한 영향을 검색하고, 그 기전을 규명코자 연구를 시행하여 다음과 같은 연구결과를 얻었다. Forskolin (1.0 uM)은 흰쥐 부신적출정맥내로 1분동안 관류시킨 후 Ach(50 ug), excess $K^+$(56 mM), DMPP (100 uM) 및 caffeine (0.3 mM)에 의한 CA 분비작용을 현저히 증강시켰으나 McN-A-343에 의한 CA분비작용에는 영향을 미치지 않았다. Forskolin 자체는 CA분비작용을 일으키지 못하였다. 또한 세포의 calcium을 제거한 상태에서도 위 약물에 의한 CA분비작용에 대하여 유의한 증강작용을 나타내었다. 그러나 McN-A-343의 CA작용에는 영향이 없었으나 위의 약물의 CA분비작용을 유의하게 강화시켰다. Cyclic AMP를 증가시키는 약물로 알려져 있는 dibutyryl cyclic AMP (DBcAMP)는 300 uM농도를 1분간 관류시 Ach, excess $K^+$ 및 DMPP의 CA 분비작용을 뚜렷하게 증강시켰으나 McN-A-343 및 caffeine의 CA분비에는 별다른 영향이 없었다. DBcAMP 자체도 CA분비작용에는 영향을 미치지 못하였으나 또한 DBcAMP는 세포의 칼슘제거시에도 위의 약물에 의한 CA분비작용을 의의있게 증강시켰다. 그렇지만, McN-A-343의 CA분비작용은 증강시키지 못하였다. 이상의 연구결과로 보아 Forskolin는 adenylate cyclase를 활성화 시킴으로써 cyclic AMP 농도를 증가시켜 세포내로 칼슘유입을 증강시키며, 또한 세포내의 칼슘이동에도 관여함으로써 cholinergic nicotinic stimulation 및 depolarization에 의한 CA분비작용을 상승시키는 것으로 사료되어진다.

• The Korean Journal of Physiology and Pharmacology
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• 제13권3호
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• pp.229-239
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• 2009

The aim of the present study was to examine the effect of provinol, which is a mixture of polyphenolic compounds from red wine, on the secretion of catecholamines (CA) from isolated perfused rat adrenal medulla, and to elucidate its mechanism of action. Provinol (0.3 ${\sim}$ 3 ${\mu}g/ml$) perfused into an adrenal vein for 90 min dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}M$) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}M$). Provinol itself did not affect basal CA secretion. Also, in the presence of provinol (1 ${\mu}g/ml$), the secretory responses of CA evoked by Bay-K-8644 (a voltage-dependent L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}M$), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}M$) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}M$) were significantly reduced. Interestingly, in the simultaneous presence of provinol (1 ${\mu}g/ml$) plus L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}M$), the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid recovered to the considerable extent of the corresponding control secretion in comparison with the inhibition of provinol-treatment alone. Under the same condition, the level of NO released from adrenal medulla after the treatment of provinol (3 ${\mu}g/ml$) was greatly elevated in comparison to its basal release. Taken together, these data demonstrate that provinol inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the perfused rat adrenal medulla. This inhibitory effect of provinol seems to be exerted by inhibiting the influx of both calcium and sodium into the rat adrenal medullary cells along with the blockade of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of nitric oxide synthase.