• Natural Product Sciences
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• 제27권2호
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

• 한국발생생물학회지:발생과생식
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• 제6권2호
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• pp.105-110
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• 2002

포유동물의 생식을 조절하는 다수의 호르몬 가운데 가장 중요한 것들로 난소로부터의 estrogen과 progesterone을 들 수 있다. 반면 다양한 스트레스 인자들은 암컷의 성 반응 행동과 번식을 억제함이 잘 알려졌다. 이러한 스트레스가 가해지는 동안 부신에서는 카테콜아민(catecholamine)이 다량 분비되어 위기 상황에 대처하며 이 과정에서 생식 현상의 억제가 일어나는 것으로 추정된다. 본 연구에서는 생식호르몬 분비와 성 행동 양식에 광범위한 영향을 미침이 알려진 카테콜아민 중 특히 부신의 norepinephrine(NE)과 epinephrine(E) 합성ㆍ분비 양상과 발정주기 간의 상관관계를 조사하였다. 이를 위해 HPLC-ECD를 사용하여 주기 중인 흰쥐 부신 수질내 NE와 E함량과 체외 배양한 부신으로부터의 분비를 조사하였다. NE 함량은 proestrus에서 증가하기 시작하여 diestrus I에서 최고에 도달하였고, diestrus II에 최소치로 감소하였다. 부신 내 E 함량의 최고치는 proestrus, 그리고 최저치는 diestrus II에서 관찰되었다. 흰쥐 부신 내 NE : E ratio는 diestrus I에서 1 : 4.81로 가장 낮았고 기타 시기에는 1 : 6.13～7.02였다. 체외 배양한 흰쥐 부신으로부터의 NE 분비는 diestrus II에서 가장 낮았으며 estrus에서 최고에 도달하였고, proestrus에서의 분비 역시 diestrus II 때보다 유의성있게 높았다. E분비의 최고치는 estrus에서, 그리고 최저치는 diestrus 떼서 II 관찰되었다. 한편 배양액 중 Ne : E ratio는 estrus에서 1 : 3.32로 가장 높았고 기타 시기에는 1 : 2.34～2.65였다. 본 연구 결과는 (1) 흰쥐 부신에서 카테콜아민 생성과 분비 양상이 발정주기 중 역동적으로 변화하며, (2) NE로부터 E로의 전환이 발정주기 중 stage-specific하게 일어남을 나타내는 것으로서, 이는 카테콜아민 합성율을 결정하는 rate limiting enzyme인 tyrosine hydroxylase(TH)와 NE에서 E로의 전환 과정을 매개하는 phenylethanolamine-N-methyltransferase(PNMT)의 발현과 활성이 중추신경계에서와 유사하게 생식호르몬, 특히 estrogen and/or progesterone의 영향을 받음을 시사한다.

• The Korean Journal of Physiology and Pharmacology
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• 제6권4호
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• pp.215-223
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• 2002

The present study was undertaken to investigate the effect of doxorubicin (DX) on secretion of catecholamines (CA) evoked by ACh, high $K^+,$ DMPP and McN-A-343 from the isolated perfused rat adrenal gland and to establish the mechanism of its action. DX $(10^{-7}{\sim}10^{-6}\;M)$ perfused into an adrenal vein for 60 min produced relatively dose- and time-dependent inhibition of CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP $(10^{-4}\;M)$ and McN-A-343 $(10^{-4}\;M).$ However, lower dose of DX did not affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M),$ but its higher doses depressed time-dependently CA secretion evoked by high $K^+.$ DX itself did also fail to affect basal CA output. In adrenal glands loaded with DX $(3{\times}10^{-7}\;M),$ CA secretory responses evoked by Bay-K-8644, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}-ATPase$ were time-dependently inhibited. Furthermore, daunorubicin $(3{\times}10^{-7}\;M),$ given into the adrenal gland for 60 min, attenuated CA secretory responses evoked by ACh, high $K^+,$ DMPP and McN-A-343. Taken together, these results suggest that DX causes relatively dose- and time-dependent inhibition of CA secretory responses evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors from the isolated perfused rat adrenal gland. However, lower dose of DX did not affect CA secretion by high $K^+,$ and higher doses of DX reduced time-dependently CA secretion of high $K^+.$ It is thought that these effects of DX may be mediated by inhibiting both influx of extracellular calcium into the rat adrenomedullary chromaffin cells and intracelluar calcium release from the cytoplasmic store. Also, there was no difference in the mode of action between DX and daunorubicin in rat adrenomedullary CA secretion.

• 대한약리학회지
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• 제29권1호
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• pp.43-55
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• 1993

흰쥐 관류부신에서 histamine의 catecholamine (CA) 분비작용의 특성과 기전을 규명코자 연구한 결과는 다음과 같다. Histamine $(37.5{\sim}150\;{\mu}g)$을 부신정맥내에 주사 하였을 때 현저한 용량 의존성의 CA 분비작용을 나타내었다. 그러나 histamine $(150\;{\mu}g)$을 120분 간격으로 반복 투여시 제 3차 투여시부터는 CA 분비효과가 뚜렷이 감소하였다. 즉, histamine의 반복투여로 인한 반응급강현상을 관찰할 수 있었다. Histamine의 CA 분비작용은 chlorisondamine, diphenhydrarmine, ranitidine, $Ca^{++}-free$ Krebs 용액의 관류, nicardipine 및 TMB-8 등의 전처치로 유의하게 억제 되었으나 pirenzepine의 전처치에 의해서는 별다른 영향을 받지 않았다. 더우기 histamine $(6.8{\times}10^{-5}M)$으로 30분간 관류시킨 후에 ACh $(50{\mu}g)$의 CA 분비작용이 상당히 억제됨을 나타내었다. 이상과 같은 연구 결과로 보아 histamine은 흰쥐 적출관류 부신에서 현저한 CA 분비작용을 나타내었으며 칼슘 의존성이었다. 이러한 CA 분비작용은 $H_1-$ 및 $H_2-$ 양수용체의 활성화를 통해서 일어나며 또한 부신의 nicotine 수용체와도 관련성이 있는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.259-270
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• 2001

The present study was attempted to investigate the characteristics of epibatidine on secretion of catecholamines (CA) from the isolated perfused model of the rat adrenal gland, and to establish the mechanism of action. Epibatidine $(3{\times}10^{-8}\;M)$ injected into an adrenal vein produced a great inhibition in secretory response of CA from the perfused rat adrenal gland. However, upon the repeated injection of epibatidine $(3{\times}10^{-8}\;M)$ at 15 min-intervals, CA secretion was rapidly decreased after second injection of epibatidine. However, there was no statistical difference between CA secretory responses of both 1st and 2nd periods by the successive administration of epibatidine at 120 min-intervals. Tachyphylaxis to releasing effects of CA evoked by epibatidine was observed by the repeated administration. Therefore, in all subsequent experiments, epibatidine was not administered successively more than twice only 120 min-intervals. The epibatidine-induced CA secretion was markedly inhibited by the pretreatment with atropine, chlorisondamine, pirenzepine, nicardipine, TMB-8, and perfusion of $Ca^{2+}-free$ Krebs solution containing EGTA, while was not affected by diphenhydramine. Moreover, the CA secretion evoked by ACh for 1st period $(0{\sim}4\;min)$ was greatly potentiated by the simultaneous perfusion of epibatidine $(1.5{\times}10^{-8}\;M),$ but followed by time-dependently gradual reduction after 2nd period. The CA release evoked by high potassium $(5.6{\times}10^{-8}\;M),$ for 1st period $(0{\sim}4\;min)$ was also enhanced by the simultaneous perfusion of epibatidine, but those after 2nd period were not affected. Taken together, these experimental data suggest that epibatidine causes catecholamine secretion in a calcium dependent fashion from the perfused rat adrenal gland through activation of neuronal cholinergic (nicotinic and muscarinic) receptors located in adrenomedullary chromaffin cells. It also seems that epibatidine-evoked catecholamine release is not relevant to stimulation of histaminergic receptors.

• Archives of Pharmacal Research
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• 제26권9호
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• pp.747-755
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• 2003

The aim of the present study was to clarify whether cotinine affects the release of catecholamines (CA) from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, in comparison with the response of nicotine. Cotinine (0.3∼3 mM), when perfused into an adrenal vein for 60 min, inhibited CA secretory responses evoked by ACh (5.32 mM), DMPP (a selective neuronal nicotinic agonist, 100 $\mu$M for 2 min) and McN-A-343 (a selective muscarinic $M_1 -agonist, 100 \mu$ M for 2 min) in dose- and time-dependent manners. However, cotinine did not affect CA secretion by high $K^+$ (56 mM). Cotinine itself also failed to affect basal CA output. Furthermore, in the presence of cotinine (1 mM), CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, 10 $\mu$ M) and cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase, 10 \mu$ M) were relative time-dependently attenuated. However, nicotine (30$\mu$ M), given into the adrenal gland for 60 min, initially rather enhanced CA secretory responses evoked by ACh and high $K^+$, followed by the inhibition later, while it time-dependently depressed the CA release evoked by McN-A-343 and DMPP. Taken together, these results suggest that cotinine inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by the direct membrane-depolarization. It seems that this inhibitory effect of cotinine may be exerted by the cholinergic blockade, which is associated with blocking both the calcium influx into the rat adrenal medullary chromaffin cells and $Ca^{2+}$ release from the cytoplasmic calcium store. It also seems that there is a big difference in the mode of action between cotinine and nicotine in the rat adrenomedullary CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• 제18권5호
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• pp.431-439
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• 2014

The aim of the present study was to investigate whether ginsenoside-Rb2 (Rb2) can affect the secretion of catecholamines (CA) in the perfused model of the rat adrenal medulla. Rb2 ($3{\sim}30{\mu}M$), perfused into an adrenal vein for 90 min, inhibited ACh (5.32 mM)-evoked CA secretory response in a dose- and time-dependent fashion. Rb2 ($10{\mu}M$) also time-dependently inhibited the CA secretion evoked by DMPP ($100{\mu}M$, a selective neuronal nicotinic receptor agonist) and high $K^+$ (56 mM, a direct membrane depolarizer). Rb2 itself did not affect basal CA secretion (data not shown). Also, in the presence of Rb2 ($50{\mu}g/mL$), 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 Rb2 ($10{\mu}M$) and L-NAME (an inhibitor of NO synthase, $30{\mu}M$), the inhibitory responses of Rb2 on ACh-evoked CA secretory response was considerably recovered to the extent of the corresponding control secretion compared with the inhibitory effect of Rb2-treatment alone. Practically, the level of NO released from adrenal medulla after the treatment of Rb2 ($10{\mu}M$) was greatly elevated compared to the corresponding basal released level. Collectively, these results demonstrate that Rb2 inhibits the CA secretory responses evoked by nicotinic stimulation as well as by direct membrane-depolarization from the isolated perfused rat adrenal medulla. It seems that this inhibitory effect of Rb2 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.

• The Korean Journal of Physiology and Pharmacology
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• 제13권6호
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• pp.517-526
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• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a 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. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.

• The Korean Journal of Physiology and Pharmacology
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• 제12권3호
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• pp.101-109
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• 2008

The aim of the present study was to examine the effects of ketamine, a dissociative anesthetics, on secretion of catecholamines (CA) secretion evoked by cholinergic stimulation from the perfused model of the isolated rat adrenal gland, and to establish its mechanism of action, and to compare ketamine effect with that of thiopental sodium, which is one of intravenous barbiturate anesthetics. Ketamine ($30{\sim}300{\mu}M$), perfused into an adrenal vein for 60 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 NN receptor agonist, $100{\mu}M$) and McN-A-343 (a selective muscarinic M1 receptor agonist, $100{\mu}M$). Also, in the presence of ketamine ($100{\mu}M$), the CA secretory responses evoked by veratridine (a voltage-dependent $Na^+$ channel activator, $100{\mu}M$), 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, thiopental sodium ($100{\mu}M$) also caused the inhibitory effects on the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, veratridine, Bay-K-8644, and cyclopiazonic acid. Collectively, these experimental results demonstrate that ketamine inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland. It seems likely that the inhibitory effect of ketamine is mediated by blocking the influx of both $Ca^{2+}$ and $Na^+$ through voltage-dependent $Ca^{2+}$ and $Na^+$ channels into the rat adrenal medullary chromaffin cells as well as by inhibiting $Ca^{2+}$ release from the cytoplasmic calcium store, which are relevant to the blockade of cholinergic receptors. It is also thought that, on the basis of concentrations, ketamine causes similar inhibitory effect with thiopental in the CA secretion from the perfused rat adrenal medulla.

• 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.