• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.128-128
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• 2003

Bradykinin modulates the sympathetic system in various ways. It can stimulate sympathetic neurotransmission directly through presynaptic receptors (Llona et al., 1991) and indirectly via its hypotensive or nociceptive effects which activate central and ganglionic mechanisms (Kuo and Keeton, 1991; Dray et al., 1988). However, it has been found that bradykinin can also liberate prostaglandins in peripheral tissues, thereby attenuating the release of catecholamines(Starke et al., 1977). (omitted)

• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.443-454
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• 1998

The present study was attempted to investigate the effect of vasoactive intestinal polypeptide (VIP) on secretion of catecholamines (CA) and to establish whether there is the existence of a noncholinergic mechanism in adrenomedullary CA secretion from the isolated perfused rat adrenal gland. The perfusion into an adrenal vein of VIP $(3{\times}10^{-6}\;M)$ for 5 min or the injection of acetylcholine (ACh, $5.32{\times}10^{-3}\;M$) resulted in great increases in CA secretion. Tachyphylaxis to releasing effect of CA evoked by VIP was not observed by the repeated perfusion. The net increase in adrenal CA secretion evoked by VIP still remained unaffected in the presence of atropine or chlorisondamine. However, the CA release in response to ACh was greatly inhibited by the pretreatment with atropine or chlorisondamine. The releasing effects of CA evoked by either VIP or ACh were depressed by pretreatment with nicardipine, TMB-8, and the perfusion of $Ca^{2+}$-free medium. Moreover, VIP- as well as ACh-evoked CA secretory responses were markedly inhibited under the presence of $(Lys^1,\;Pro^{2.5},\;Arg^{3.4},\;Tyr^6)-VIP$ or naloxone. CA secretory responses induced by ACh and high $K^+\;(5.6{\times}10^{-2}\;M)$ were potentiated by infusion of VIP $(3{\times}10^{-6}M\;for\;5\;min)$. Taken together, these experimental results indicate that VIP causes CA release in a fashion of calcium ion -dependence, suggesting strongly that there exists a noncholinergic mechanism that may be involved in the regulation of adrenomedullary CA secretion through VIP receptors in the rat adrenal gland, and that VIP may be the noncholinergic excitatory secretagogue present in the chromaffin cells.

• Biomolecules & Therapeutics
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• 제16권2호
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• pp.147-160
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• 2008

The present study was designed to examine effects of polyphenolic compounds isolated from red wine (PCRW) on the release of catecholamines (CA) from the isolated perfused model of the rat adrenal medulla, and to clarify its mechanism of action. PCRW (20${\sim}$180 ${\mu}$g/mL), given into an adrenal vein for 90 min, caused inhibition of 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) in dose- and time-dependent fashion. PCRW itself did not affect basal CA secretion (data not shown). Following the perfusion of PCRW (60 ${\mu}$g/mL), the secretory responses of CA evoked by Bay-K-8644 (a 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 also markedly blocked, respectively. Interestingly, in the simultaneous presence of PCRW (60 ${\mu}$g/mL) and L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}$M), the inhibitory responses of PCRW on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid were recovered to considerable level of the corresponding control release compared with those effects of PCRW-treatment alone. Practically, the amount of NO released from adrenal medulla after loading of PCRW (180 ${\mu}$g/mL) was significantly increased in comparison to the corresponding basal released level. Collectively, these results obtained here demonstrate that PCRW 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 gland of the normotensive rats. It seems that this inhibitory effect of PCRW is mediated by blocking the influx of both ions through $Na^+$ and $Ca^+{2$} channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are due at least partly to the increased NO production through the activation of nitric oxide synthase. Based on these data, it is also thought that PCRW may be beneficial to prevent or alleviate the cardiovascular diseases, such as hypertension and angina pectoris.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1988년도 학술대회지
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• pp.55-62
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• 1988

본 연구에서 한국산 인삼의 활성성분의 하나인 panaxadiol(PD)의 가토적출분신에서 카테콜아민(CA)의 분비작용과 작용기전을 파악하고자 실험을 시행하여 다음과 같은 결과를 얻었다. PD($400\;{\mu}g$)을 가토적출부신에 투여 하였을 때 카테콜아민의 분비를 유의성 있게 증가시켰다. PD의 이러한 CA분비작용은 atiropine처리로 현저히 억제되었다. Physostigmine 처리시 PD뿐만 아니라 Ach의 CA 분비작용은 뚜렷이 증가 되었다. 그러나 chlorisondamine처리로 PD나 Ach의 분비효과는 억제되었다. 또한 PD($400\;{\mu}g$/30min)을 주입한 후에 Ach의 CA분비작용은 증강되었다. Ouabain에 의해서 PD의 작용은 약화되었으나 Ach의 CA분비효과는 오히려 강화되었다. PD나 Ach의 작용은 adenosine 전처리시 현저히 증강되었다. EDTA(5mM)와 함께 Ca-free Krebs액으로 30분 주입한 경우에 Ach의 분비작용은 거의 전적으로 차단되었으며, PD의 작용도 약화되었다. 이상의 실험결과로 보아, PD는 가토적출부신에서 $Ca^{++}$의존적으로 CA분비를 증가시키며, PD의 이러한 작용은 부신내의 cholinergic muscarinic 및 nicotinic receptor의 흥분작용에 기인되고, chromaffin cell에 대한 일부 직접작용에 의해서 나타나는 것으로 사료된다.

• 대한약리학회지
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• 제30권3호
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• pp.299-311
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• 1994

Pentazocine은 opioid 수용체에 대한 흥분작용과 길항작용을 겸유한 opioid계 약물로 알려져 있다. 본 연구에서 흰쥐 적출 관류부신으로 부터 pentazocine의 catecholamine(CA) 분비작용을 관찰하여 그 기전을 규명하고 또한 다른 opioid의 작용과 비교하여 얻어진 결과는 다음과 같다. Pentazocine$(30{\sim}300\;ug)$을 부신정맥내에 주사하였을때 현저한 용량의 존성의 CA 분비작용을 나타내었다. Pentazocine의 이러한 CA 분비작용은 chlorisondamine $(10^{-6}\;M)$, naloxone $(1.22{\times}10^{-7}\;M)$, morphine $(1.73{\times}10^{-5}\;M)$, enkephalin $(9.68{\times}10^{-6}\;M)$, nicardipine $(10^{-6}\;M)$ 및 TMB-8$(10^{-5}\;M)$등의 전처치로 뚜렷이 억제되었으나 pirenzepine (2과$10^{-6}\;M)$의 전처치에 의해서는 영향을 받지 않았다. $Ca^{++}$-free Krebs 용액으로 30분간 관류한 후에 pentazocine의 CA 분비작용은 현저한 감소를 나타냈었다. Pentazocine $(1.75{\times}10^{-4}\;M)$을 20분간 관류시킨 후에 ACh $(5.32{\times}10^{-3}\;M)$과 DMPP $(10^{-4}\;M)$에 의한 CA 분비작용이 의의 있게 감약되었다. 이상과 같은 연구결과를 종합하면, pentazocine은 횐쥐 적출 관류부신에 투여시 현저한 CA 분비작용을 일으키고 있는 칼슘의존성 exocytotic mechanism에 의한 것으로 생각되며, 이러한 pentazocine의 CA 분비작용은 부신 chromaffin cell에 있는 opioid 수용체의 활성화를 통하여 나타나며, 또한 부신의 nicotine 수용체의 흥분작용과도 관련성이 있는 것으로 사료된다.

• 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.148-149
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• 1998

It has been known that potassium channel openers are a new class of molecules that have attracted general interest because of their potent antihypertensive activity in vivo and vasorelaxant activity in vitro (Hamilton and Weston, 1989). In the present study, it was attempted to examine the effect of the potassium channel opener on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. The perfusion of pinacidil (30-300 uM) into an adrenal vein for 20 min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.32 mM), high $K^{+}$ (56 mM), DMPP (100 uM for 2 min), McN-A-343 (100 uM for 2 min), cyclopiazonic acid (10 uM for 4 min) and Bay-K-8644 (10 uM for 4 min). Also, under the presence of minoxidil (100 uM), which is also known to be a potassium channel activator, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly depressed. However, in adrenal glands preloaded with pinacidil (100 uM) under the presence of glibenclamide (1 uM), an antidiabetic sulfonylurea that has been shown to be a specific blocker of ATP-regulated potassium channels (for 20 min), CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were considerably recovered to a considerable extent of the normal release as compared to that of pinacidil only. These results, taken together, suggest that pinacidil cause the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating strongly that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells. Furthermore, these findings suggest strongly that these potassium channel openers-sensitive membrane potassium channels also play an important role in regulating CA secretion.

• The Korean Journal of Physiology and Pharmacology
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• 제12권1호
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• pp.13-23
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• 2008

The aim of the present study was designed to establish comparatively the inhibitory effects of $D_1$-like and $D_2$-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 $(30{\mu}M)$ and R-(-)-TNPA $(30{\mu}M)$ perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M)$, DMPP $(10^{-4}\;M)$, McN-A-343 $(10^{-4}\;M)$, high $K^+$ $(5.6{\times}10^{-2}\;M)$, Bay-K-8644 $(10{\mu}M)$, and cyclopiazonic acid $(10{\mu}M)$, respectively. For the release of CA evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a selectve $D_1$-like dopaminergic receptor antagonist, and S(-)-raclopride, a selectve $D_2$-like dopaminergic receptor antagonist, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid only for $0{\sim}4$ min. The rank order for the enhancement of CA release evoked by high $K^+$, McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride. Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)-SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)-TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland without affecting the basal release, respectively, but both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them. It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are mediated by the activation of $D_1$-like and $D_2$-like dopaminergic receptors located on the rat adrenomedullary chromaffin cells, respectively, whereas the facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the blockade of $D_1$-like and $D_2$-like dopaminergic receptors, respectively: this action is possibly associated with extra- and intracellular calcium mobilization. Based on these results, it is thought that the presence of dopaminergic $D_1$ receptors may play an important role in regulation of the rat adrenomedullary CA secretion, in addition to well-known dopaminergic $D_2$ receptors.

• 대한약리학회지
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• 제30권1호
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• pp.87-100
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• 1994

도파민 함유세포가 교감신경절에 존재하는 것으로 알려져 있으나, 말초에서 신경전달 물질로써 그의 역할과 작용기전에 대해서 아직까지 알려진 바가 많지 않다. 따라서 본 연구에서는 도파민 $D_2$-수용체의 선택적인 효능약으로 알려진 apomorphine이 흰쥐 적출 관류 부신에서 카테콜아민(CA)분비작용에 미치는 영향을 연구코자 시도하여 다음과 같은 연구결과를 얻었다. $10{\um}M\;Apomorphine$의 비교적 낮은 농도를 부신정맥내에 20분간 관류 하였을때 5.32mM ACh, 56mM KCl, $100{\mu}M$ DMPP 및 $100{\mu}M$ McN-A-343 등의 투여에 의한 CA 분비작용이 의의 있게 감소되었다. Apomorphine 농도를 $30{\mu}M$로 증가시켜 관류하였을때 상기약물에 의한 CA 분비작용은 더욱 억제되었으며 또한 Bay-K-8644에 의한 $100{\mu}M$의 고농도로 전처치 하였을때, ACh, excess $K^+$, DMPP 및 McN-A-343에 의한 CA분비작용은 현저히 차단되었다. 도파민 $D_2$-수용체 차단제인 metoclopramide $(30{\mu}M)$으로 20분간 관류 하였을때 ACh, DMPP 및 McN-A-343에 의한 CA 분비작용은 유의하게 억제된 효과를 나타내었으나 $excess\;{K^+}$에 의한 CA분비작용은 별다른 영향을 받지 않았다. 그러나 metoclopramide $(30{\mu}M)$ 존재하에서 $30{\mu}M$ apomorphine으로 20분간 전처치 하였을때 $excess{K^+}$ 뿐만 아니라 DMPP의 CA 분비작용은 별다른 변화를 받지 않았다. 이상과 같은 실험 연구결과를 종합하여 보면, apomorphine은 cholinergic receptor stimulation과 membrane depolarization에 의한 CA 분비작용을 용량의존적으로 억제하여, 이러한 작용은 억제성 도파민 수용체를 활성화 시킴으로써 흰쥐 부신 수질의 chromaffin cell 내로 칼슘의 유입을 억제하여 나타나는 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제7권4호
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• pp.231-238
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• 2003

The present study was undertaken to investigate the effect of bradykinin on secretion of catecholamines (CA) evoked by stimulation of cholinergic receptors and membrane depolarization from the isolated perfused model of the rat adrenal glands, and to elucidate its mechanism of action. Bradykinin $(3{\times}10^{-8}M)$ alone produced a weak secretory response of the CA. however, the perfusion with bradykinin $(3{\times}10^{-8}M)$ into an adrenal vein of the rat adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by ACh $(5.32{\times}10^{-3}M)$, excess $K^+$ ($5.6{\times}10^{-2}M$, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic agonist) and McN-A-343 ($10^{-4}$ M, a selective M1-muscarinic agonist). Moreover, bradykinin ($3{\times}10^{-8}$ M) in to an adrenal vein for 90 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels. However, in the presence of $(N-Methyl-D-Phe^7)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_2$-bradykinin receptor, bradykinin no longer enhanced the CA secretion evoked by Ach and high potassium whereas the pretreatment with Lys-$(des-Arg^9,\;Leu^9)$-bradykinin trifluoroacetate salt $(3{\times}10^{-8}M)$, an antagonist of $BK_1$-bradykinin receptor did fail to affect them. Furthermore, the perfusion with bradykinin $(3{\times}10^{-6}M)$ into an adrenal vein of the rabbit adrenal gland for 90 min enhanced markedly the secretory responses of CA evoked by excess $K^+$ $(5.6{\times}10^{-2}M)$. Collectively, these experimental results suggest that bradykinin enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization through the activation of $B_2$-bradykinin receptors, not through $B_1$-bradykinin receptors. This facilitatory effect of bradykinin seems to be associated to the increased $Ca^{2+}$ influx through the activation of the dihydropyridine L-type $Ca^{2+}$ channels.