• Proceedings of the PSK Conference
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• 2003.04a
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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)

• The Korean Journal of Pharmacology
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• v.28 no.2
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• pp.181-190
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• 1992

The present study was conducted to investigate the effect of opioids on catecholamine (CA) secretion evoked by a selective cholinergic nicotinic agonist, 1,1-dimethyl-4-phenyl piperazinium (DMPP) and acetylcholine from the retrogradely perfused rat adrenal glands. Methionine-enkephalin $(9.68{\times}10^{-6}\;M)$ caused a significant inhibition of CA secretion evoked by DMPP (100 uM) and $ACh\;(50\;{\mu}g)$, but had no effect on the spontaneous (basal) CA release. Morphine $(1.73{\times}10^{-5}\;M)$ attenuated considerablely the increase in CA release induced by DMPP and ACh. Morphine itself also did not affect the basal CA output. A 20 to 65% reduction of the DMPP- and ACh-evoked increase in CA release was observed after the pretreatment with methionine-enkephalin or morphine. The increase in CA release evoked by DMPP and ACh was reduced markedly by preloading with an opiate antagonist naloxone $(1.22{\times}10^{-7}\;M)$ while basal CA output was not affected by naloxone. These present experimental results suggest that the nicotinic stimulation-evoked CA release from the perfused rat adrenal gland is inhibited by endogenously released opioid peptides through activation of opiate receptors located in the adrenal gland.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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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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• v.16 no.2
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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.

• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.55-62
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• 1988

The effect of panaxadiol (PD). an active component of Korean ginseng saponins on the secretion of catecholamines (CA) from the rabbit adrenal gland and its mode of action were investigated. PD ($400\;{\mu}g$) increased significantly the secretion of CA from the isolated perfused rabbit adrenal gland. PD-induced secretion of CA was reduced markedly by treatment with atropine. CA secretion induced by Ach or PD was potentiated by physostigmine treatment. Chlorisondamine inhibited CA secretion of PD or Ach. Perfusion of PD ($400\;{\mu}g$) for 30 minutes enhanced the secretory activity of CA by Ach. Ouabain weakened the secretory rsponse caused by PD but enhanced the response by Ach. Adenosine treatment resulted in marked increase in CA secretion by PD or Ach. Perfusion with calcium free Krebs solution containing 5 mM EDTA for 30 minutes completely blocked the secretory effect induced by Ach and also weakened that evoked by PD. It is suggested that PD causes the secretion of CA from the rabbit adrenal gland by a calcium dependent exocytotic process. The secretory effect of PD is due to the stimulation of cholinergic muscarinic and nicotinic-receptors present in the adrenal gland partly by direct action on the chromaffin cell.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.299-311
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• 1994

The present study was attempted to investigate whether pentazocine, which is known to possess both opioid agonistic and antagonistic properties, produces catecholamines (CA) secretion from the isolated perfused rat adrenal gland, and to establish the mechanism of its action, and also to compare its action with that of some opioids. Pentazocine (30 to 300 ug) injected into an adrenal vein caused a dose-dependent secretory response of CA from the rat adrenal medulla. The pentazocine-evoked secretion of CA was remarkably diminished by the preloading with chlorisondamine $(10^{-6}\;M)$, naloxone $(1.22{\times}10^{-7}\;M)$, morphine $(1.7{\times}10^{-5}\;M)$, met-enkephalin $(9.68{\times}10^{-6}\;M)$, nicardipine $(10^{-6}\;M)$ and TMB-8 $(10^{-5}\;M)$ while was not influenced by the pretreatment of pirenzepine $(2{\times}10^{-6}\;M)$. The perfusion of $Ca^{++}$-free Krebs solution for 30 min into the gland also led to the marked reduction in CA secretion evoked by pentazocine. Furthermore, the CA release evoked by ACh and/or DMPP was greatly inhibited by the pretreatment with pentazocine $(1.75{\times}10^{-4}\;M)$ for 20 min. From these experimental results, it is thought that pentazocine causes markedly the increased secretion of CA from the isolated perfused rat adrenal medulla by a calcium-dependent exocytotic mechanism. The secretory effect of pentazocine appears to be mediated through activation of opioid receptors located on adrenal chromaffin cells, which may be also associated with stimulation of cholinergic nicotinic receptors.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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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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• v.12 no.1
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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.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.87-100
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• 1994

It has been known for some time that dopamine-containing cells are existed in sympathetic ganglia, i.e., small, intensely fluorescent cells. However, its role and mechanism of action as a peripheral neurotransmitter are poorly understood so far. In the present study, an attempt was made to examine the effect of apomorphine, which is known to be a selective agonist of dopaminergic $D_2$. receptor on secretion of catecholamines (CA) from the isolated perfused rat adrenal gland. The perfusion of a low concentration of 10uM apomorphine into an adrenal vein for 20 min produced significant reduction in CA secretion induced by 5.32 mM ACh, 56 mM KCl, 100 uM DMPP and 100 uM McN-A-343. Increasing apomorphine concentration to 30 uM led to more markedly decreased CA secretion as compared to the case of 10 uM apomorphine and also did inhibit clearly CA release by $10^{-5}M$ Bay-K-8644. Furthermore, in adrenal glands preloaded with a higher dose of 100 uM apomorphine, CA releases evoked by ACh, excess $K^+$, DMPP and McN-A-343 were almost abolished by the drug. The perfusion of $3.3{\pm}10^{-5}M$ metoclopramide, which is well-known as a selective dopaminergic $D_2$ antagonist, produced significantly inhibitory effect of CA release by ACh, DMPP and McN-A-343 but did not affect that by excess $K^+$. However, preloading of 30uM apomorphine in the presence of metoclopramide did not modify the CA secretory effect of excess $K+$ and DMPP. These experimental results demonstrate that apomorphine causes dose-dependent inhibition of CA secretion by cholinergic receptor stimulation and also by membrane depolarization from the isolated perfused rat adrenal gland, suggesting that these effects appear to be exerted by inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells through activation of inhibitory dopaminergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.4
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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.