• 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.

• BMB Reports
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• 제35권4호
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• pp.420-427
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• 2002

Partial nerve injury is the main cause of neuropathic pain disorders in humans. Acupuncture has long been used to relieve pain. It is known to relieve pain by controlling the activities of the autonomic nervous system. Although the mechanism of neuropathic pain and analgesic effects of electroacupuncture (EA) have been studied in a rat model system, its detailed mechanism at the molecular level remains unclear. To identify genes that might serve as either markers or explain these distinct biological functions, a cDNA microarray analysis was used to compare the expression of 8,400 genes among three sample groups. Messenger RNAs that were pooled from the spinal nerves of 7 normal. 7 neuropathic pain, and 7 EA treatment rat models were compared. Sixty-eight genes were differentially expressed more than 2-fold in the neuropathic rat model when compared to the normal, and restored to the normal expression level after the EA treatment. These genes are involved in a number of biological processes, including the signal transduction, gene expression, and nociceptive pathways. Confirmation of the differential gene expression was performed by a dot-blot analysis. Dot-blotting results showed that the opioid receptor sigma was among those genes. This indicates that opioid-signaling events are involved in neuropathic pain and the analgesic effects of EA. The potential application of these data include the identification and characterization of signaling pathways that are involved in the EA treatment, studies on the role of the opioid receptor in neuropathic pain, and further exploration on the role of selected identified genes in animal models.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1990년도 Proceedings of International Symposium on Korean Ginseng, 1990, Seoul, Korea
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• pp.36-44
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins. The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponins intracerebrally or intrathecally The development of morphine tolerance and dependence, and the abrupt expression of naloxone induced abstinence syndrome were also inhibited by ginsenoside Kbl , Rba, Rgl and Re. These results suggest that ginsenoside Kbl, Rba, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence syndrome. In addition, further research on the minor components of Panax ginseng should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain level of monoamines at the various time intervals and at the various day intervals, respectively The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum (U-receptor) and mouse was definers (5·receptor) were not mediated through opioid receptors. The antagonism of a x receptor agonist, U-, iO.488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, bolt mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine S-dehydrogenase that catalyzed the production of morphine from morphine, and increased hepatic glutathione contents for the detoxification of morphine. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• 대한약리학회지
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• 제30권1호
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• pp.11-18
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• 1994

Opioid수용체는 adenylate cyclase의 활성을 억제하므로써 cyclic AMP의 양을 감소시킨다. 본 연구에서는 striatum에서 dopamine과 opioid 신경전달계의 상호관계를 알아보고자 haloperidol(750ug/kg)을 10일간 복강내 투여하여 dopaminergic pathway를 차단시킨후 mouse striatum에서 선택적 opioid ${\mu},\;{\gamma}\;{\kappa}$ 수용체 agonist들에 의해 축적되는 cAMP양을 측정하여 본 결과, haloperidol단독투여에 의해서 cAMP는 유의한 증가를 나타내었으며, haloperidol 장기투여된 mouse striatum 에서 morphine(20mg/kg), DAGO(5Oug/kg), DPDPE(50ug/kg), U5O,488H (500ug/kg)투여에 의해서 haloperidol에 의한 cAMP 증가는 억제되었으며, 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 비해서는 DAGO, DPDPE 투여군에서 증가를 나타내었다. Haloperidol장기투여로 인한 morphine, DAGO, DPDPE, U5O,488H의 영향은 naloxone에 의해서 morphine과 U5O, 488H투여군에서 길항되었으며 정상 mouse에 투여된 morphine, DAGO, DPDPE, U5O,488H에 의한 cAMP의 감소는 naloxone에 의하여 모든 실험군에서 길항되었다. 이상의 결과로 보아 dopaminergic denervation시 mouse striatum에서 ${\mu},\;{\gamma},\;{\kappa}$효현제에 의하여 축적되는 cAMP양은 ${\kappa}$수용체 효현제인 U5O,488H에서 가장 현저한 감소를 보여 각 수용체의 활성화정도는 변화되며, 그중에서 ${\kappa}$수용체는 그 기능이 가장 보존되고 있음을 알 수 있었다.

• The Korean Journal of Pain
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• 제22권1호
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• pp.58-64
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• 2009

Background: Magnesium is a noncompetitive antagonist of the N-methyl-D aspartate (NMDA) receptor. Magnesium is thought to be involved in opioid tolerance by way of inhibiting calcium entry into cells. Methods: The patients were randomly assigned to three groups according to the anesthetic regimens: Group M received magnesium sulfate and Group C received saline intravenously under remifentanil-based anesthesia. Group S received saline intravenously under sevoflurane based anesthesia in place of remifentanil. The patients in the group M received 25% magnesium sulfate 50 mg/kg in 100 ml of saline, and those patients in groups C and S received an equal volume of saline before induction of anesthesia; this was followed by 10 mg/kg/h infusion of either magnesium sulfate (group M) or an equal volume of saline (groups C and S) until the end of surgery. Pain was assessed on a visual analog scale at 1, 6, 12, 24, and 36 hours after the operation. The time to the first postoperative analgesic requirement and the cumulative analgesic consumption were evaluated in the three groups. Results: The visual analog scales for pain and the cumulative analgesic consumption were significantly greater in group C than in other groups. The time to first postoperative analgesic requirement was significantly shorter in group C than that in the other groups. There were no differences between group M and S for side effects. Conclusions: A relatively high dose and continuous remifentanil infusion is associated with clinically relevant evidence of acute opioid tolerance. NMDA-receptor antagonist, magnesium sulfate as an adjuvant analgesic prevents opioid tolerance in patients who are undergoing major abdominal surgery under high dose and continuous remifentanil infusion-based anesthesia.

• Advances in Traditional Medicine
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• 제6권3호
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• pp.186-195
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• 2006

The present study was carried out to determine the involvement of opioid and non-opioid receptor and the effect of pH and enzymes on the recently reported antinociceptive activity of aqueous extract of Corchorus olitorius (AECO) leaves using the abdominal constriction test. The extract was prepared by soaking the dried powdered leaves of Corchorus (C.) olitorius in distilled water overnight, and the supernatant obtained was considered as a stock solution with 100% concentration/ strength. The extract, administered subcutaneously in the concentrations/ strength of 10, 50 and 100%, was found to show a significant concentration-independent antinociception. The 50% concentration AECO were further used to study on the above mentioned parameters. The extract exhibited: significant (P < 0.05) decreased in activity when pre-treated (s.c.) against 10 mg/kg naloxonazine, bicuculine (10 mg/kg), phenoxybenzamine (10 mg/kg), 10 mg/kg pindolol, and 5 mg/kg mecamylamme, but not 10 mg/kg naltrindole, 10 mg/kg atropine, respectively; significant (P < 0.05) decreased in activity after pre-treatment against 10% a-amylase, but not 1 % protease or 10% lipase and; significant (P < 0.05) decreased in activity after exposure to alkaline condition (pH between 9 and 13) while maintaining the activity at acidic condition, respectively. The C. olitorius leaves antinociception, which involved, at least in part, activation of $\mu-opioid,\;\alpha-and\;\beta-adrenergic$, and nicotinic receptors, was found to decrease under alkaline condition and in the presence of $\alpha-amylase$.

• 생물정신의학
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• 제6권2호
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• Journal of Acupuncture Research
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• 제22권3호
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• pp.23-35
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• 2005

본 연구에서는 전침자극이 면역계의 THl/TH2 분화평형에 미치는 영향과 opioid system 과의 관계를 알아보고자 DNP-KLH의 자극을 통해 IgE 매개 알러지 반응모델을 구축하고 족삼리(足三里).에 전침자극을 가한 후 TH1/TH2 분화평형 및 opioid receptor antagonist인 naloxone에 의 한 반전여부를 확인하기 위해 total IgE, antigen-specific IgE, IFN-${\gamma}$ 및 IL-4 mRNA 발현량을 측정하여 다음과 같은 결과를 얻었다. 1. 전침자극은 DNP-KLH로 인해 과도하게 생산 된 혈청 total IgE 및 antigen-specific IgE를 감소시킴으로서 알러지 반응에 대한 유의한 억제능을 발휘하였으며, naloxone 투여로 전침 의 효과가 상쇠된 것으로 미루어 opioid system이 전침에 의한 항알러지 효과에 중요한 역할을 하는 것으로 추정된다. 2. 또한 전침자극은 DNP-KLH로 인한 TH2 cytokine의 편향상태에 대하여 TH1/TH2 평형조절능을 가진다는 것을 확인하였으며, naloxone으로 반전되지 않는 것으로 미루어 전침이 미치는 보조 T cell 분화에 대한 효과 는 opioid system에 의존하지 않는 것으로 추정된다.

• 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.110.1-110.1
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• 2002