• Biomolecules & Therapeutics
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• 제8권4호
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• pp.338-348
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• 2000

The present study was attempted to determine the effect of 5'-(N'-ethylcarboxamido) adenosine (NECA), which is an potent $A_2$-adenosine receptor agonist, on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. NECA (20 nM) perfused into the adrenal vein for 60 min produced a time-related inhibition in CA secretion evoked by ACh (5.32x10$^{-3}$ M), high $K^{+}$(5.6x10$^{-2}$ 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). Also, in the presence of $\beta$,${\gamma}$-methylene adenosine-5'-triphosphate (MATP), which is also known to be a selective $P_{2x}$-purinergic receptor agonist, showed a similar inhibition elf CA release evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. However, in adrenal glands preloaded with 20$\mu$M NECA for 20 min under the presence of 20$\mu$M 3-isobutyl-1-methyl-xanthine (IBMX), an adenosine receptors antagonist, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were much recovered in comparison to the case of NECA-treatment only. Taken together, these results indicate that NECA causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization. This inhibitory effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells through the adenosine receptor stimulation. Therefore, it is suggested that the inhibitory mechanism of adenosine receptor stimulation may play a modulatory role in regulating CA secretion.n.n.

• The Korean Journal of Physiology and Pharmacology
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• 제3권3호
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• pp.339-350
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• 1999

The present study was attempted to examine the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on catecholamine (CA) secretion evoked by cholinergic stimulation, membrane depolarization and calcium mobilization from the isolated perfused rat adrenal gland. The perfusion of PACAP (10 nM) into an adrenal vein for 60 min produced a great 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 $(10^{-5}\;M\;for\;4\;min).$ Also, in the presence of neuropeptide (NPY), which is known to be co-localized with norepinephrine in peripheral sympathetic nerves, 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 PACAP (10 nM) under the presence of VIP antagonist $[(Lys^1,\;Pro^{2.5},\;Arg^{3.4},\;Tyr^6)-VIP\;(3\;{\mu}M)]$ for 20 min, CA secretory responses evoked by ACh, high potassium, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were not altered greatly in comparison to the case of PACAP-treatment only. Taken together, these results suggest that PACAP causes the marked inhibition of CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as by membrane depolarization, indicating that this effect may be mediated by inhibiting influx of extracellular calcium and release in intracellular calcium in the rat adrenomedullary chromaffin cells.

• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.265-272
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• 2004

The present study was attempted to investigate the effect of cilnidipine (FRC-8635), which is a newly synthesised novel dihydropyridine (DHP) type of organic $Ca^{2+}$ channel blockers, on secretion of catecholamines (CA) evoked by acetylcholine (ACh), high $K^+$, DMPP and McN-A-343 from the isolated perfused rat adrenal gland. Cilnidipine $(1{\sim}10{\mu}M)$ perfused into an adrenal vein for 60 min produced relatively dose- and time-dependent 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 $(10^{-4}M\;for\;2\;min)$. However, lower dose of cilnidipine did not affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M)$, higher dose of it reduced greatly CA secretion of high $K^{+}$. Cilnidipine itself did fail to affect basal catecholamine output. In the presence of cilnidipine $(10{\mu}M)$, the CA secretory responses evoked by Bay-K-8644 $(10{\mu}M)$, an activator of L-type $Ca^{2+}$ channels and cyclopiazonic acid $(10{\mu}M)$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase were also inhibited. Moreover, ${\omega}-conotoxin\;GVIA\;(1{\mu}M)$, a selective blocker of the N-type $Ca^{2+}$ channels, given into the adrenal gland for 60 min, also inhibited time-dependently CA secretory responses evoked by Ach, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid. Taken together, these results demostrate that cilnidipine inhibits CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors from the isolated perfused rat adrenal gland without affecting the basal release. However, at lower dose, cilnidipine did not affect CA release by membrane depolarization while at larger dose inhibited that. It seems likely that this inhibitory effect of cilnidipine is exerted by blocking both L- and N-type voltage-dependent $Ca^{2+}$ channels (VDCCs) on the rat adrenomedullary chromaffin cells, which is relevant to inhibition of both the $Ca^{2+}$ influx into the adrenal chromaffin cells and intracellular $Ca^{2+}$ release from the cytoplasmic store. It is thought that N-type VDCCs may play an important role in regulation of CA release from the rat adrenal medulla.

• 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.

• 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.147-147
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• 1998

The present study was designed to examine the effect of total ginseng saponin on CA secretion evoked by activation of nicotinic receptors from the isolated perfused rat adrenal glands. Total ginseng saponin given (100 $\mu\textrm{g}$/20 min) into an adrenal vein did fail to produce alteration of spontaneous CA release from the rat adrenal medulla. Acetylcholine (5.32 mM)- and DMPP (100 uM, a selective ncotinic receptor agonist)-evoked CA secretory responses were reduced markedly by the pretreatment with the total ginseng saponin at a rate of 100 $\mu\textrm{g}$/6.2 $m\ell$/20 min, respectively.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.106.1-106.1
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• 2002

• 한국가축번식학회지
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• 제4권1호
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• pp.47-74
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• 1980

The present experiments were carried out to elucidate the effects of hypophysectomy and subsequent administration of sex hormone on thyroid, adrenal gland, gonads and blood plasma components in the rat. The jresults obtained were summarized as follows: The weight of the thyroid gland of both male and female hypophysectiomzed rats decreased markedly from 7 days up to 56 days after the hypophysectomy as compared to the control group. The administration of sex hormone (6 mg of testosterone propionate to male and 6 mg of hexestrol to female) to the hypophysectomized rat gave on effect on the change in the weight of the thyroid gland. The hopophysectomy decreased the uptake of radioactive iodine in the thyroid gland in both male and female rats with time. Subsequent administration of the sex hormone caused no effect. With regard to the histological changes of the thyroid gland, the hypophysectomy caused significant changes in the gland showing a remarkable degeneration. The function of the gland seemed to disa, pp.ar almost completely on 56th day after the hypophysectomy. Upon the administration of sex hormone after the hypophysectomy, however. the epithelia of the follicle which has changed to flat from has partly returned to its functional cubicfrom and nuclei recovered as nearly as normal. These recovery were more remarkable in the female than in the male. The hypophysectomy kept causing a significant decrease in the weight of the adrenal gland in male and female rats during the period of observation (up to 56 days) as in the case of thyroid gland. The administration of sex hormone has on effect in this respect either. The hypophysectomy also caused a marked morphological change in the gland: zona fasciculata and zona reticularis were dicreased in size quichly after the hypophysectomy. The administraton of the sex hormone to the hypophysectomized rat resulted in clear distinction among the three layers of the adrenal cortex which otherwise very diffused. In the male, this phenomenum was more remarkable than in the female and the pattern of the cell arrangements and the thickening of each layer became similar to those of normal rats. The gonads of both sexes have also kept decreasing in the weight and degenerated in morpohology after the hypophysectomy. However, the degenerate follicle became enlarged after the administration of hexestrol in the female. Furthermore, the vacuoles found in interstitial cells of hypophysectomized rat disa, pp.ared after the administration of testosterone in the male and the formation of spermatocytes seemed to be recovered. Hypophysectomy also caused a gradual increase in the contents of total protein, non-protein nitrogen, total lipid, cholesterol and calcium in the blood plasma with time. The concentrations of sodium, potassium and chloride in the blood did not change after the hypophysectomy. Sex hormone caused practically no change in above tendency.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.223-230
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• 2005

The purpose of the present study was to examine the effect of naltrexone, an opioid antagonist, on secretion of catecholamines (CA) evoked by cholinergic nicotinic stimulation and membrane-depolarization from the isolated perfused rat adrenal gland and to establish the mechanism of its action. Naltrexone $(3{\times}10^{-6}M)$ perfused into an adrenal vein for 60 min produced time-dependent inhibition in CA secretory responses evoked by ACh $(5.32{\times}10^{-3}M)$ , high $K^+$ $(5.6{\times}10^{-2}M)$ , DMPP ($10^{-4}$ M) and McN-A-343 $(10^{-4}M)$ . Naltrexone itself did also fail to affect basal CA output. In adrenal glands loaded with naltrexone $(3{\times}10^{-6}M)$ , the 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 also inhibited. However, in the presence of met-enkephalin $(5{\times}10^{-6}M)$ , a well-known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Collectively, these experimental results demonstrate that naltrexone inhibits greatly CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that this inhibitory effect of naltrexone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• Archives of Pharmacal Research
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• 제28권6호
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• pp.699-708
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• 2005

The present study was designed to investigate the effect of naloxone, a well known opioid antagonist, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal glands, and to establish its mechanism of action. Naloxone ($10^{-6}\~10^{-5}$ M), perfused into an adrenal vein for 60 min, produced dose- and time-dependent inhibition of CA secretory responses evoked by ACh ($5.32\times10^{-3}$ M), high K+ ($5.6\times10^{-2}$ M), DMPP ($10^{-4}$ M) and McN-A-343 ($10^{-4}$ M). Naloxone itself also failed to affect the basal CA output. In adrenal glands loaded with naloxone ($3\times10^{-6}$ M), the 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 also inhibited. In the presence of met-enkephalin ($5\times10^{-6}$ M), a well known opioid agonist, the CA secretory responses evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid were also significantly inhibited. Taken together, these results suggest that naloxone greatly inhibits the CA secretion evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors as well as that by membrane depolarization. It seems that these inhibitory effects of naloxone does not involve opioid receptors, but might be mediated by blocking both the calcium influx into the rat adrenal medullary chromaffin cells and the uptake of $Ca^{2+}$ into the cytoplasmic calcium store, which are at least partly relevant to the direct interaction with the nicotinic receptor itself.

• 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.75.2-75.2
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• 2003

The present study was designed to compare the effects of conotoxin GVIA, a selective blocker of N-type voltage-dependent calcium channels (VDCC) and cilnidipine, a blocker of both L- and N-type VDCC, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused rat adrenal gland, and also to establish the mechanism of action. 1. The inhibition of the CA secretory response evoked by acetylcholine (5.32 x 10$\^$-3/ ${\mu}$M) was stronger in cilnidipine-treated glands than in conotoxin GVIA-treated glands. (omitted)