• The Korean Journal of Physiology and Pharmacology
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• 제10권5호
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• pp.273-282
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• 2006

The aim of the present study was to investigate the effects of R-(-)-2,10,11-trihydroxy-N-propylnoraporphine [R-(-)-TNPA], a selective agonist of dopaminergic $D_2$ receptor and S(-)-raclopride, a selective antagonist of dopaminergic $D_2$ receptor, on the secretion of catecholamines (CA) evoked by cholinergic stimulation and membrane-depolarization in the isolated perfused model of the rat adrenal gland, and also to establish its mechanism of action. R-(-)-TNPA $(10{\sim}100\;{\mu}M)$ perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. R-(-)-TNPA itself did also fail to affect basal CA output. Also, in adrenal glands loaded with R-(-)-TNPA $(30\;{\mu}M)$, 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. However, S(-)-raclopride $(1{\sim}10\;{\mu}M)$, given into an adrenal vein for 60 min, enhanced the CA secretory responses evoked by ACh, high $K^+$, DMPP and McN-A-343 only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, S(-)-raclopride $(3.0\;{\mu}M)$ in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644 and cyclopiazonic acid only for the first period (4 min). However, after simultaneous perfusion of R-(-)-TNP A $(30\;{\mu}M)$ and S(-)-raclopride $(3.0\;{\mu}M)$, the inhibitory responses of R(-)-TNPA $(30\;{\mu}M)$ on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644, and cyclopiazonic acid were significantly reduced. Taken together, these experimental results suggest that R-(-)-TNPA greatly inhibits the CA secretion from the perfused rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) and membrane depolarization, but S(-)-raclopride rather enhances the CA release by them. It seems that this inhibitory of R-(-)-TNPA may be mediated by stimulation of inhibitory dopaminergic $D_2$ receptors located on the rat adrenomedullary chromaffin cells, while the facilitatory effect of S(-)-raclopride is due to the blockade of dopaminergic $D_2$ receptors, which are relevant to extra- and intracellular calcium mobilization. Therefore, it is thought that dopaminergic $D_2$ receptors may be involved in regulation of CA release in the rat adrenal medulla.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.115-125
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• 1992

An attempt was made to investigate the effect of TMB-8[3, 4, 5-trimethoxybenzoate-8 (N, N-diethylamino) octyl ester], which is known to be an inhibitor of intracellular $Ca^{2+}$ release, on catecholamines (CA) secretion evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine from the isolated perfused rat adrenal glands and to cleaify its mechanism of action. The pretreatment with a low dose of TMB-8 $(10 \mu{M)}$ for 20 min led to marked inhibition in CA secretion evoked by Ach (5.32 mM), excess K^+$ (56 mM), DMPP $(100\;\mu{M)}$, McN-A-343 $(100 \mu{M)}$ and BAY-K 8644 $(10^{-5}M)$. Caffeine-induced CA secretion was simimlar to that of control only during the first periods (0-3 min) but thereafter maked inhibition in CA secretion evoked by caffeine was observed during the rest periods up to 30 min. The increased moderate concentration of TMB-8 $(30 \;\mu{M)}$ caused the result similar to that of $10 \;\mu{M}$ TMB-8. However, in adrenal glands preloaded with a high dose of TMB-8 $(100\;\mu{M)}$, CA releases evoked by Ach, excess $K^+$, DMPP, McN-A-343 and caffeine were almost completely blocked by the drug. These experimental data demonstrate that TMB-8 may inhibit cholinergic receptor-mediated and also depolarization-dependent Ca secretion, suggenesting that these TMB-8 effects seem to be mediated through inhibiting influx of extracellular calcium into the rat adrenal medullary chromaffin cells as well as reducing the release of calcium from intracellular sources.

• 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.

• 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.

• 한국수의병리학회지
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• 제1권1호
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• pp.13-25
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• 1997

The anticarcinogenic effects of dimethyl disulfide(DMDS, methyl disulfide)and diallyl disulfide(DADA, allyl disulfide) were studied in a 28 weeks rat multi-organ carcinogenesis model. neoplastic and preneoplastic lesions were observed in the liver kidney thyroid gland esophagus duodenum colon, rectum and adrenal gland. Tesults showed that neoplastic lesions in the kidney liver and thyroid gland were inhibited by DADS but those in the liver and colon were enhanced by DMDS when compared to positive control group. incidence of neoplastic lesions in the other organs were not changed by DMDS or DADS exposure. While GST-p positive foci in the liver were increased by DMDS, DADS had no effect. There was no significant histopathological lesion in DMDS or DADS treated group without pretreatment with carcinogens.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.95-95
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• 2001

Ciinidipine (FRC-8635) is a newly synthesized novel DHP type of organic Ca$\_$2＋/channel blockers that have been developed so far in Japan (Yoshimoto et al., 1991 : Hosono et at., 1992). It also has a blocking action on L-type voltage-dependent Ca$\^$2＋/channel (VDCCs) in the rabbit basilar artery (Oike et al., 1990) and a slow-onset and long-lasting hypotensive action in clinical and experimental studies (Ikeda et al., 1992 ; Tominaga et al., 1997). Recent electrophysiological data indicate that cilnidipine might be a dual-channel antagonist for peripheral neuronal N-type and vascular L-type Ca$\^$2＋/channels (Oike et al., 1990 ; Fujii et al., 1997; Uneyama et at., 1997). However, little is known about the involvement of N-type VDCCs in contributing to the muscarinic receptor-mediated CA secretion. Therefore, the present study was attempted to investigate the effect of cilinidipine on secretion of catecholamines (CA) evoked by ACh, high K$\^$＋/, DMPP and McN-A-343 from the isolated perfused rat adrenal gland. Cilnidipine (1-10 ${\mu}$M) perfused into an adrenal vein for 60 min produced dose- and time-dependent inhibition in CA secretory responses evoked by ACh (5.32${\times}$10$\^$-3/M), DMPP (10$\^$-4/ M for 2 min) and McN-A-343 (10$\^$-4/ M for 2 min). However, lower dose of lobeline did not affect CA secretion by high K$\^$＋/(5.6${\times}$10$\^$-2/ M), higher dose of it reduced greatly CA secretion of high K$\^$＋/. Cilnidipine itself did also fail to affect basal catecholamine output. Furthermore, in adrenal glands loaded with cilnidipine (10 ${\mu}$M), CA secretory response evoked by Bay-K-8644 (10 ${\mu}$M), an activator of L-type Ca$\^$2＋/channels was markedly inhibited while CA secretion by cyclopiazonic acid (10 ${\mu}$M), an inhibitor of cytoplasmic Ca$\^$2＋/-ATPase was no affected. Moreover, $\omega$-conotoxin GVIA (1 ${\mu}$M), given into the adrenal gland for 60 min, also inhibited time-dependently CA secretory responses evoked by ACh and high K$\^$＋/.

• 한국가축번식학회지
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• 제4권1호
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• pp.35-45
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• 1980

The purpose of this experiment was to investigate the effects of castration and administration of testosterone propionate(TP) on the development of the thyroid, adrenal glands and the testis in immature male rats, 25 days immatured, weighing 64.1${\pm}$2g, were divided into two groups of control and castrated, each sub-divided into 30 rats again, treated and untreated with TP respectivity. Each rat was given 20$m\ell$ of TP subcutaneously at two weeks interval. Six rats among each group were randomly sacrificed at 7, 21, 35, 49, and 63 days after treatment, of which their thyroid, adrenal glands and testis were collected for cytometric observation. The results obtained were as follows. 1. The size of the follicle of thyroid glands had a tendency to increase proportionally to the treatment period in every group. However, in castration group, the follicular size of the untreated with TP were significantly increased from 49 days (p<0.05) after treatment than that of the treated with TP, while in control group, the treated with TP were not increased during the treatment period. Regarding the height of the follicular epithelial cell in thyroid gland, the treated with TP had a tendency to increase than the untreated with TP in both castration and control group. 2. Regarding the size of the follicle of thyroid gland in relation with the increment period, the untreated with TP in control group were slightly increased from 49 days after treatment, but the treated with TP were not changed significantly. Castration group had a tendency to increase significantly than the control group, especially the untreated with TP in castration group were significantly increased. 3. As for the change of the relative height of thyroidal follicular epithelial cell in relation with the increment of treatment period, the untreated, A and C group, in both castration and control group were increased at 35 days 63 days after treatment while the treated, B and D group had tendency to increase from 21 days after treatment. 4. Regarding the thickness fo adrenal cortex, the castration group had a tendency to increase than the control group until 21 days after treatment. But, at 35 days, the change of the thickness was reversed; Mean while at 49 days and 63 days, especially C group in castration were significantly increased than any other groups although there were no significant differences among the every group during the whole treatment period. Regarding the thickness of adrenal cortex in relation with the increment of treatment period, A, B and C group had a tendency to increase until 21 days after treatment. After that period, there was no significant increment in all groups. Especially, in D group, there were no significant changes from 7 days to 63 days after treatment. 5. As for the tickness of adrenal medulla, there were no significant changes in every group of castration and TP treatment, except that the castration group had a tendency to increase continually than the control throughout the whole treament period. 6. In terms of the number, diameter and thickness of seminiferous tubule in testis of control group, the treated group with TP were distinctly reduced than those of the untreated group from 49 days after treatment respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제12권4호
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• pp.155-164
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• 2008

Resveratrol has been known to possess various potent cardiovascular effects in animal, but there is little information on its functional effect on the secretion of catecholamines (CA) from the perfused model of the adrenal medulla. Therefore, the aim of the present study was to determine the effect of resveratrol on the CA secretion from the isolated perfused model of the normotensive rat adrenal gland, and to elucidate its mechanism of action. Resveratrol (10${\sim}100{\mu}$M) during perfusion into an adrenal vein for 90 min inhibited 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 both a time- and dose- dependent fashion. Also, in the presence of resveratrol (30${\mu}$M), the secretory responses of CA evoked by veratridine 8644 (an activator of voltage-dependent$Na^+$ channels, 100${\mu}$M), Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10${\mu}$M), and cyc1opiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10${\mu}$M) were significantly reduced. In the simultaneous presence of resveratrol (30${\mu}$M) and L-NAME (an inhibitor of NO synthase, 30${\mu}$M), the CA secretory evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyc1opiazonic acid were recovered to a considerable extent of the corresponding control secretion compared with the inhibitory effect of resveratrol alone. Interestingly, the amount of nitric oxide (NO) released from the adrenal medulla was greatly increased in comparison to its basal release. Taken together, these experimental results demonstrate that resveratrol can inhibit the CA secretory responses evoked by stimulation of cholinergic nicotinic receptors, as well as by direct membrane-depolarization in the isolated perfused model of the rat adrenal gland. It seems that this inhibitory effect of resveratrol is exerted by inhibiting an influx of both ions through $Na^+$ and $Ca^{2+}$ channels into the adrenomedullary cells as well as by blocking the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are mediated at least partly by the increased NO production due to the activation of NO synthase.

• 대한약리학회지
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• 제27권2호
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• pp.167-181
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• 1991

Adenylate cyclase 효소를 활성화시키는 약물인 Forskolin의 흰쥐 적출관류 부신으로부터 Ach, excess $K^+$, McN-A-343 및 caffein에 의한 catecholamines (CA) 분비작용에 대한 영향을 검색하고, 그 기전을 규명코자 연구를 시행하여 다음과 같은 연구결과를 얻었다. Forskolin (1.0 uM)은 흰쥐 부신적출정맥내로 1분동안 관류시킨 후 Ach(50 ug), excess $K^+$(56 mM), DMPP (100 uM) 및 caffeine (0.3 mM)에 의한 CA 분비작용을 현저히 증강시켰으나 McN-A-343에 의한 CA분비작용에는 영향을 미치지 않았다. Forskolin 자체는 CA분비작용을 일으키지 못하였다. 또한 세포의 calcium을 제거한 상태에서도 위 약물에 의한 CA분비작용에 대하여 유의한 증강작용을 나타내었다. 그러나 McN-A-343의 CA작용에는 영향이 없었으나 위의 약물의 CA분비작용을 유의하게 강화시켰다. Cyclic AMP를 증가시키는 약물로 알려져 있는 dibutyryl cyclic AMP (DBcAMP)는 300 uM농도를 1분간 관류시 Ach, excess $K^+$ 및 DMPP의 CA 분비작용을 뚜렷하게 증강시켰으나 McN-A-343 및 caffeine의 CA분비에는 별다른 영향이 없었다. DBcAMP 자체도 CA분비작용에는 영향을 미치지 못하였으나 또한 DBcAMP는 세포의 칼슘제거시에도 위의 약물에 의한 CA분비작용을 의의있게 증강시켰다. 그렇지만, McN-A-343의 CA분비작용은 증강시키지 못하였다. 이상의 연구결과로 보아 Forskolin는 adenylate cyclase를 활성화 시킴으로써 cyclic AMP 농도를 증가시켜 세포내로 칼슘유입을 증강시키며, 또한 세포내의 칼슘이동에도 관여함으로써 cholinergic nicotinic stimulation 및 depolarization에 의한 CA분비작용을 상승시키는 것으로 사료되어진다.

• 대한약리학회지
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• 제32권1호
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• pp.83-91
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• 1996

본 연구에서는 Hydrocortisone이 적출 흰쥐 관류 부신에서 histamine에 의한 카테콜아민 (CA) 분비작용에 대한 영향을 관찰하고자 시도하였으며, 얻어진 연구 결과는 다음과 같다. Histamine (150ug)은 부신정맥내로 주입시 현저한 CA 분비작용을 나타내었다. 이러한 histamine의 CA 분비작용은 천연 글루코콜티코이드인 hydrocortisone (30uM)이나 합성 글루코콜티코이드인 dexamethasone (30uM)을 각각 20분간 전처치한 후에 현저히 증강되었다. Hydrocortisone에 의한 histamine의 CA 분비의 증강작용은 inositol trisphosphate 수용체 억제제인 heparin (3.56U/ml)으로 천처치시 뚜렷이 억제되었으나 adenylate cyclase의 강력한 활성화제인 forskolin (0.2uM)으로 전처치시 현저히 강화되었다. 이상과 같은 실험 결과를 종합한 결과, hydrocortisone (글루코콜티코이드)은 흰쥐 적출관류 부신에서 histamine의 CA 유리작용을 증강시킬 수 있으며, 이는 부신수질 크롬친화성 세포에서 inositol phosphate 뿐만 아니라 cyclic AMP의 축적작용과 관련성이 있는것으로 사료된다.