• 한국의학물리학회지:의학물리
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• 제8권1호
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• pp.3-15
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• 1997

Adrenal chromaffin cells secrete catecholamine in response to acetylcholine. The secretory response has absolute requirement for extracellular calcium, indication that $Ca^{2+}$ influx through voltage dependent $Ca^{2+}$ channel (VDCC) is the primary trigger of the secretion cascade. Although the existence of various types of $Ca^{2+}$ channels has been explored using patch clamp technique in adrenal chromaffin cells, the contribution of different types of $Ca^{2+}$ channels to catecholamine secretion remains to be established. To investigate the quantative contribution of different types of $Ca^{2+}$ channels to cate-cholamine secretion, $Ca^{2+}$ current($I_{Ca}$) and the resultant membrane capacitance increment($\Delta{C}_{m}$) were simultaneoulsy measured. Software based phasor detector technique was used to monitor $\Delta{C}_{m}$. After blockade of L type VDCC with nicardipine (1$\mu$M), $I_{ca}$ was blocked to 43.85$\pm$6.72%(mean$\pm$SEM) of control and the resultant ㅿC$_{m}$ was reduced ot 30.10$\pm$16.44% of control. In the presence of nicardipine and $\omega$-conotoxin in GVIA(l$\mu$M), an N type VDCC antagonist, $I_{ca}$ was blocked to 11.62$\pm$2.96% of control and the resultant $\Delta{C}_{m}$ was reduced to 26.13$\pm$8.25% of control. Finally, in the presence of L, N, and P type $Ca^{2\pm}$ channel antagonists(nicardipine, $\omega$-Conotoxin GVIA, and $\omega$-agatoxin IVA, respectively), $I_{ca}$ and resultant $\Delta{C}_{m}$ were almost completely blocked. From the observation of parallel effects of $Ca^{2+}$ channel antagonists on $I_{ca}$ and $\Delta{C}_{m}$, it was concluded that L, N, and also P type $Ca^{2+}$ channels served and $Ca^{2+}$ source for exocytosis and no difference was observed in their efficiency to evoke exocytosis amost L, N, and P type $Ca^{2+}$ channels.

• 대한약리학회지
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• 제28권2호
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• pp.181-190
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• 1992

흰쥐 적출관류 부신에서 선택적인 nicotine 수용체 효능약인 DMPP(1,1-dimethyl-4-phenylpiperazinium)와 acetylcholine(ACh)의 카테콜아민(CA) 분비작용에 대한 opioids의 영향을 연구하고자 시행하여 얻어진 연구결과는 다음과 같다. Methionine-enkephalin$(9.68{\times}10^{-6}\;M)$으로 전처치시 DMPP(100 uM)과 $ACh(50\;{\mu}g)$에 의한 CA 유리작용이 현저히 억제되었으며 basal CA release는 영향을 받지 않았다. Morphine$(1.73{\times}10^{-5}\;M)$으로 전처치시 DMPP 및 excess $K^+$의 CA 분비작용은 뚜렷이 약화되었다. Morphine 역시 그자체는 basal CA release에는 영향을 미치지 않았다. Opiate 수용체 길항제인 naloxone$(1.22{\times}10^{-7}\;M)$은 DMPP 및 ACh에 의한 CA 분비작용을 현저히 차단 하였으나 basal CA release에는 영향을 미치지 못하였다. 이와 같은 연구결과로 보아, 흰쥐 관류 부신에서 니코틴 수용체에 의한 CA 분비작용은 내인성 opioid peptide에 의해서 억제되며, 이는 부신에 존재하는 opiate 수용체 흥분작용에 기인되는 것으로 사료된다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.40-46
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• 1998

We investigated the influence of the root of Panax ginseng C. A. Meyer on the secretion of catecholamines from bovine adrenal chromaffin cells, which are used as a model of nervous systems. In two major parts extracted from the ginseng root, the crude saponin fraction, but not the non-saponin fraction, reduced the secretion from the cells, stimulated by acetylcholine (ACh). Ginseng saponins (ginsenosides) are classified into three groups, the panaxadiol, the panaxatriol and the oleanolic acid groups, on the basis of the chemical structures of their saponins. Both the panaxadiol and the panaxatriol saponins, excluding only one oleanolic acid saponin ginsenoside-Ro, generally reduced the ACh-evoked secretion. The inhibitory effects of the panaxatriol were much stronger than those of the panaxadiol. However, ginsenoside-Rg, and -Rh3 in the panaxadiol saponins were the potent inhibitors comparable to the panaxatriol saponins. Ginsenoside-Rg2 in the panaxatriol was the most effective. It is probable that the ginsenoside inhibition of the catecholamine secretion is due to the suppression of the function of the nicotinic ACh receptor-cation channels. On the other hand, ginsenoside-Rg2 did not affect the angiotensin II-, the bradykinin-, the histamine- and the neurotensin- induced catecholamine secretions from the chromaffin cells and the muscarine- and the histamine- induced contraction of the ileum in guinea-pigs. Ginsenoside-Rbl, a panaxadiol saponin, and ginsenoside-Ro had no or only a slight effect on them. On the contrary, ginsenoside-Rg3 not only competitively inhibited the muscarine-induced ileum contraction but also reduced the angiotensin R -, the bradykinin-, the histamine- and the neurotensin-induced catecholamine secretions. Thus, the ginseng root contains active ingredients, namely some ginsensides, which suppress the responses induced by receptor stimulation. The inhibitory effects of ginseng saponins may be one of the action mechanisms for the pharmacological effects of the Panax ginseng root.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제13권4호
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• pp.327-335
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• 2009

The aim of this study was to determine whether losartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor could influence the CA release from the isolated perfused model of the rat adrenal medulla. Losartan (5${\sim}$50 ${\mu}$M) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}$M) and McN-A-343 (100 ${\mu}$M). Losartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with losartan (15 ${\mu}$M) for 90 min, the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}$M, an activator of L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}$M, an inhibitor of cytoplasmic $Ca^{2+}$ -ATPase), veratridine (100 ${\mu}$M, an activator of $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations (150${\sim}$300 ${\mu}$M), losartan rather enhanced the CA secretion evoked by ACh. Collectively, these experimental results suggest that losartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla, but at high concentration it rather inhibits ACh-evoked CA secretion. It seems that losartan has a dual action, acting as both agonist and antagonist to nicotinic receptors of the rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of losartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement of the CA release.

• 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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.83.2-83.2
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• 2003

It has been demonstrated the presence of leptin receptors (Ob-Ra) on epinephrine-secreting chromaffin cells in rat adrenal medulla, suggesting that leptin may directly affect the adrenal medulla (Cao et al., 1997). Leptin is found to stimulate catecholamine (CA) synthesis in cultured bovine adrenal medullary cells (Utsumomiya et al., 2001; Shibuya et al., 2002)and cultured porcine adrenal medullary cells (Takekoshi et al., 2001). Thus, the present study was designed to examine the effect of leptin on CA release from the isolated perfused rat adrenal gland, and to establish its mechanism of action. (omitted)

• 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.

• 대한약리학회지
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• 제25권1호
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• pp.31-42
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• 1989

Metoclopramide (MCP)는 역류성식도염, 위하수증, 항암제에 의한 구토 증상을 치료하는데 사용되고 있는 dopamine수용체 차단제로 알려져 있다. 본 연구에서는 흰쥐의 적출 관류부신에서 catecholamine (CA)의 분비작용에 미치는 영향을 검토하여 다음과 같은 결과를 얻었다. MCP는 부신정맥내로 주입하였을때 용량의존적으로 CA 분비작용을 나타냈다. 이러한 MCP의 CA 분비작용은 atropine 전처치로 차단되었으나 chlorisondamine 처치에 의해서는 완전 차단되지 못하였다. MCP 분비작용은 physostigmine, adenosine, ouabain의 전처치로 현저히 증강되었다. 그러나 5mM-EGTA 함유 $Ca^{++}-free\;Krebs$ 액으로 관류하였을때 MCP의 CA 분비작용은 현저히 억제되었다. MCP (200 ug/30 min)를 관류한 실험에서는 KCI이나 acetylcholine의 CA 분비작용이 유의있게 감소되었다. 이상의 실험결과로 보아 MCP는 칼슘의존적기전에 의해 CA를 유리 시키며, 이러한 분비작용은 부신에서 nicotine수용체 보다도 muscarine수용체의 활성화에 더 기인 되는 것으로 생각되며, chromaffin cell에 대한 일분 직접작용도 개재되어 나타나는 것으로 사료된다.

• 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.