• Biomolecules & Therapeutics
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• v.10 no.3
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• pp.142-151
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• 2002

The present study was attempted to investigate the effect of apamin on catecholamine (CA) secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, cyclopiazonic acid and Bay-K-8644 from the isolated perfused rat adrenal gland and to establish the mechanism of its action. The perfusion of apamin (1 nM) into an adrenal vein for 20 min produced greatly potentiation in CA secretion evoked by ACh (5.32 $ imes$ $10^{-3}$ M), high $K^+$, (5.6 $ imes$ $10^{-2}$), DMPP ($10^{-4}$ M for 2 min), McN-A-343 ($10^{-4}$ M for 2 min), cyclopiazonic acid ($10^{-5}$ M for 4 min) and Bay-K-8644 ($10^{-5}$ M for 4 min). However, apamin itself did fail to affect basal catecholamine output. Furthermore, in adrenal glands preloaded with apamin (1 nM) under the presence of glibenclamide ($10^{-6}$ M), an antidiabetic sulfonylurea that has been shown to be a specific blocker of ATP-regulated potassium channels (for 20 min), CA secretion evoked by DMPP and McN-A-343 was not affected. However, the perfusion of high concentration of apamin (100 nM) into an adrenal vein for 20 min rather inhibited significantly CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, cyclopiazonic acid and Bay-K-8644. Taken together, these results suggest that the low concentration of apamin causes greatly the enhancement of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. These findings suggests that apamin-sensitive SK ($Ca^{2+}$) channels located in rat adrenal medullary chromaffin cells may play an inhibitory role in the release of catecholamines mediated by stimulation of cholinergic nicotinic and muscarinic receptors as well as membrane depolarization. However, it is thought that high concentration of apamin cause the inhibitory responses in catecholamine secretion evoked by stimulation of cholinergic receptors as well as by membrane depolarization from the rat adrenal gland without relevance with the SK channel blockade.

• Proceedings of the Korean Biophysical Society Conference
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• 1996.07a
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• pp.42-42
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• 1996

Adrenal chromaffin cells secrete catecholamine in response to acetylcholine. The secretory response has absolute requirement for extracellular calcium, indicating that $Ca^{2+}$ influx through voltage operated $Ca^{2+}$ channels (VOCC) is the primary trigger of the secretion cascade. Although the existence of various types of $Ca^{2+}$ channels has been explore using patch clamp techique in adrenal chromaffin cells, the contribution of different types of $Ca^{2+}$ channels to catecholamine secretion remains to be establised. (omitted)omitted)

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.43-55
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• 1993

The present study was conducted to examine the characteristics of histamine on catecholamine secretion in the isolated perfused rat adrenal gland and to clarify the mechanism of its secretory action. Histamine (37.5 to 150 ug) injected into an adrenal vein evoked a dose-dependent significant secretory response of catecholamines (CA) from the rat adrenal gland. However, upon the repeated injection of histamine (150 ug) at 120 min intervals, CA secretion was rapidly decreased after third injection of histamine. Tachyphylaxis to releasing effects of CA evoked by histamine was observed by the repeated administration. The histamine-induced CA secretion was markedly inhibited by the pretreatment with chlorisondamine, diphenhydramine, ranitidine, $Ca^{++}-free$ Krebs solution, nicardipine and TMB-8 while was not affected by pirenzepine. Moreover, the CA secretion evoked by ACh was considerably reduced by the prior perfusion of histamine $(6.8{\times}10^{-5} M)$ for 30 min. These experimental data suggest that histamine causes secretion of CA in a calcium dependent manner from the perfused rat adrenal gland and that its secretory effect is mediated through activation of both $H_1-$ and $H_2-histaminergic$ receptors located in adrenal medulla, which may be associated with stimulation of cholinergic nicotinic receptors.

• Archives of Pharmacal Research
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• v.25 no.6
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• pp.932-939
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• 2002

The aim of the present study was to determine the characteristics of cytisine on the secretion of catecholamines (CA) in isolated perfused rat adrenal glands, and to clarify its mechanism of action. The release of CA evoked by the continuous infusion of cytisine ($1.5{\times}10^{-5} M$) was time-dependently reduced from 15 min following the initiation of cytisine infusion. Furthermore, upon the repeated injection of cytisine ($5{\times}10^{-5}$), at 30 min intervals into an adrenal vein, the secretion of CA was rapidly decreased following the second injection. Tachyphylaxis to the release of CA was observed by the repeated administration of cytisine. The cytisine-induced secretion of CA was markedly inhibited by pretreatment with chlorisondamine, nicardipine, TMB-8, and the perfusion of $Ca^{2+}$-free Krebs solution, while it was not affected by pirenzepine or diphenhydramine. Moreover, the secretion of CA evoked by ACh was time-dependently inhibited by the prior perfusion of cytisine ($5{\times}10^{-6} M$). Taken together, these experimental data suggest that cytisine causes secretion of catecholamines from the perfused rat adrenal glands in a calcium-dependent fashion through the activation of neuronal nicotinic ACh receptors located in adrenomedullary chromaffin cells. It also seems that the cytisine-evoked release of catecholamine is not relevant to the activation of cholinergic M$_1$-muscarinic or histaminergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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• pp.243-251
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• 2001

The present study was attempted to investigate the effect of strychnine on catecholamine (CA) secretion evoked by ACh, high $K^+,$ DMPP and McN-A-343 from the isolated perfused rat adrenal gland. The perfusion of strychnine $(10^{-4}\;M)$ into an adrenal vein for 20 min produced great inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP $(10^{-4}\;M\;for\;2\;min)$ and McN-A-343 $(10^{-4}\;M\;for\;2\;min),$ but did not alter CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M).$ Strychnine itself did also fail to affect basal catecholamine output. Furthermore, in adrenal glands preloaded simultaneously with strychnine $(10^{-4}\;M)$ and glycine (an agonist of glycinergic receptor, $10^{-4}\;M),$ CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered to some extent when compared with those evoked by treatment with strychnine only. However, CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M)$ was not affected. Taken together, these results demonstrate that strychnine inhibits greatly the CA secretory responses evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does not affect that by membrane depolarization. It is suggested that strychnine-sensitive glycinergic receptors are localized in rat adrenal medullary chromaffin cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.284-284
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• 1994

Pentazocine은 opioid 수용체에 대한 흥분작용과 길항작용을 겸유한 opioid계 약물로 알려져 있다. 본 연구에서 흰쥐 적출 관류부신 으로 부터 pentazocine의 catecholamine (CA) 분비작용을 관찰하여 그 기전을 규명하고 또한 다른 opioid의 작용과 비교하여 얻어진 결과는 다음과 같다. Pentazocine (30-300$\mu\textrm{g}$)을 부신정맥내에 주사하였을때 현저한 용량 의존성의 CA 분비 작용을 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 (2 $\times$ $10^{-6}$M)의 전처치에 의해서는 영향을 받지 않았다. $Ca^{++}$-free Krebs 용액으로 30분간 관류한 후에 pentazocine의 CA 분비작용은 현저한 감소를 나타내었다. 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 의의있게 감약되었다.

• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.33-40
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• 2003

The present study was designed to investigate the effects of green tea extract (CUMC6335) and epigallocatechin gallate (EGCG) on secretion of catecholamines (CA) in the isolated perfused rat adrenal gland. ill the presence of CUMC6335 (100 $\mu\textrm{g}$/mL) into an adrenal vein for 60 min, CA secretory responses evoked by ACh(5.32 mM), high $K^+$ (56 mM) and Bay-K-8644 (10$\mu$M for 4 min) from the isolated perfused rat adrenal glands were greatly inhibited in a time-dependent fashion. However, EGCG (8 $\mu\textrm{g}$/mL) did not affect CA release evoked by ACh, high $K^+$ and Bay-K-8644. CUMC6335 itself did fail to affect basal catecholamine output. Taken together, these results demonstrate that CUMC6335 inhibits greatly CA secretion evoked by stimulation of cholinergic nicotinic receptors as well as by the direct membrane deplarization from the isolated perfused rat adrenal gland. It is felt that this inhibitory effect of CUMC6335 may be due to blocking action of the L-type dihydropyridine calcium channels in the rat adrenal medullary chromaffin cells, which is relevant to the cholinergic nicotinic blockade. It seems that there is a big difference in mode of action between CUMC6335 and EGCG.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.297-297
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• 1994

It has been known that adrenal corticosteroids influence the expression of adrenomedullary catecholamine-synthetizing enzymes and also suppress the emission of axonal-like processes in cultured chromaffin cells. In the present study, it was attempted ta investigate the effect of 17${\alpha}$-estradiol on catecholamine(CA) secretion evoked by acetylcholine(ACh), DMPP, McN-A-343, excess K$\^$+/ and Bay-K-8644 from the isolated perfused rat adrenal gland. The perfusion of 17${\alpha}$-estradiol (10$\^$-6/ 10$\^$-4/M) me an adrenal vein for 20min produced relatively dose-dependent inhibition in CA secretion evoked by ACh (5.5 ${\times}$ 10$\^$-3/M), DMPP (10$\^$-4/M for 2min), McN-A-343 (10$\^$-4/M for 4min) and Bay-K-8644 (10$\^$-5/M for 4min), while did not affect the CA secretory effect of high K$\^$+/(5.6 x 10$\^$-2/M). Also, in the presence of 17${\beta}$-estradiol, CA secretion of ACh, DMPP and McN-A-343 without any effect on excess K$\^$+/-evoked CA secretion. However, in adrenal glands preloaded with 17${\alpha}$-estradiol (10$\^$-5/M) plus tamoxifen (10$\^$-5/M), which is known to be a selective antagonist of estrogen receptors (for 20min), CA secretory responses evoked by ACh, DMPP and McN-A-343 were considerably recovered as compared to that of 17${\alpha}$-estradiol only, but excess K$\^$+/-induced CA secretion was not affected.

• The Korean Journal of Physiology and Pharmacology
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• v.5 no.3
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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.

• Biomolecules & Therapeutics
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• v.8 no.1
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• pp.13-21
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• 2000

The present study was designed to investigate the effect f quinidine on catecholamine (CA) secretion evoked by ACh, high $K^{+}$, DMPP, McN-A343, cyclopiazonic acid and Bay-K-8644 from the isolated perfused rat adrenal gland and to establish the mechanism of its action. The perfusion of quinidine (15-150 $\mu$M) into an adrenal vein for 60 min produced relatively dose- and time-dependent inhibition in CA secretion evoked by ACh (5.32$\times$10$^{-3}$ M), high $K^{+}$ (5.6$\times$10$^{-2}$ M), DMPP (10$^{-4}$ M for 2 min), McN-A-343 (10$^{-4}$ M for 2 min), cyclopiazonic acid (10$^{-5}$ M for 4 min) and Bay-K-8644 (10$^{-5}$ M for 4 min). Furthermore, in adrenal glands pre-loaded with quinine (5$\times$10$^{-5}$ M), CA secretory responses evoked by veratridine (10$^{-4}$ M) was time-dependently inhibited. Also, in the presence of lidocaine (10$^{-4}$ M), which is also known to be a sodium channel blocker, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclo-piazonic acid were also greatly reduced in similar fashion to that of quinidine-treatment. Taken together, these results suggest that quinidine causes greatly the 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 indicate strongly that this inhibitory action of quinidine appears to be associated to the blocking action of sodium channels at least in CA secretion from the rat adrenal gland.and.