• 대한화학회지
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• 제42권2호
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• pp.214-219
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• 1998

Dynorphin B유도체들인 $[Arg^{11},\;D-Ala^{12}]$ dynorphin B, $[D-Ala^2,\;Ala^6,\;Arg^{11},\;D-Ala^{12}]$ dynorphin B 및 dynorphin B (1-11)를 고상법으로 합성하였다.에탄올 용액에서 2%의 디비닐벤젠으로 교차결합된 파라-염화메틸폴리스티렌 수지와 Thr을 반응시켜 수지 1g당 1.20 mmol의 Thr을 치환시켰다. 모든 아미노산의 아미노기는 t-Boc기로 보호하였으며 Tyr과Arg의 곁사슬은 2,6-디클로로벤질기와 니트로기로 각각 보호하였다. 각 유도체는 DCC와HOBT를 짝지음 시약으로 사용하여 단계적 합성법으로 합성하였으며 생성물은 MeOH/MeCN (3/1)을 전개용매로 하여 Sephadex LH-20 column (2${\times}$50 cm)으로 정제하였으며 HPLC와 아미노산 분석기로 확인하였다.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.213-221
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• 2001

The amygdala is known as a site for inducing analgesia, but its action on the trigeminal nucleus has not been known well. Little information is available on the effect of dynorphin on NMDA receptor-mediated electrophysiological events in the trigeminal nucleus. The purpose of this study was to investigate the changes in the single neuron spikes at the trigeminal nucleus caused by the amygdala and the action of dynorphin on the trigeminal nucleus. In the present study, extracellular single unit recordings were made in the dorsal horn of the medulla (trigeminal nucleus caudalis) and the effects of microiontophoretically applied compounds were examined. When [D-Ala2, N-Me-Phe4, Glys5-ol]enkephalin (DAMGO, 10-25 mM), a ${\mu}-opioid$ receptor agonist, was infused into the amygdala, the number of NMDA-evoked spikes at the trigeminal nucleus decreased. However, the application of naloxone into the trigeminal nucleus while DAMGO being infused into the amygdala increased the number of spikes. Low dose (1 mM) of dynorphin in the trigeminal nucleus produced a significant decrease in NMDA-evoked spikes of the trigeminal nucleus but the NMDA-evoked responses were facilitated by a high dose (5 mM) of dynorphin. After the ${\kappa}$ receptors were blocked with naloxone, dynorphin induced hyperalgesia. After the NMDA receptors were blocked with AP5, dynorphin induced analgesia. In conclusion, dynorphin A exerted dose-dependent dual effects (increased & decreased spike activity) on NMDA-evoked spikes in the trigeminal nucleus. The inhibitory effect of the dynorphin at a low concentration was due to the activation of ${\kappa}$ receptors and the excitatory effect at a high concentration was due to activation of NMDA receptors in the trigeminal neurons.

• The Korean Journal of Pain
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• 제35권4호
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• pp.433-439
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• 2022

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). Methods: [D-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 ㎍ for all). Mechanical hypersensitivity was assessed using von Frey monofilaments. Results: Repeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity. Conclusions: Spinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

• 동의생리병리학회지
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• 제21권6호
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• pp.1543-1548
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• 2007

Recent experiments investigating the analgesic or anti-stress effects of electro-acupuncture provide extensive evidence that opioid or stress hormone system is involved in those effects, respectively. It has been also suggested that opioid or stress hormones modulate long-term memory consolidation or retrieval in animals and human subjects. This article reviews the possibilitythat electroacupuncture can modulate memory consolidation or retrieval. The release of serum cortisol is enhanced or reduced by high-frequency or low-frequency electroacupuncture, respectively. Also the release of beta endorphin and enkephalin is enhanced by low-frequency electroacupuncture and the release of dynorphin is enhanced by high-frequency electroacupunture. The memory consolidation is enhanced by post-training injection of Glucocorticoids, Naloxone or Dynorphin. So this review suggests strongly that memory consolidation can be modulated by electroacupuncture.

• The Korean Journal of Physiology and Pharmacology
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• 제15권2호
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• pp.95-100
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• 2011

DREAM (downstream regulatory element antagonistic modulator) is a calcium-binding protein that regulates dynorphin expression, promotes potassium channel surface expression, and enhances presenilin processing in an expression level-dependent manner. However, no molecular mechanism has yet explained how protein levels of DREAM are regulated. Here we identified group I mGluR (mGluR1/5) as a positive regulator of DREAM protein expression. Overexpression of mGluR1/5 increased the cellular level of DREAM. Up-regulation of DREAM resulted in increased DREAM protein in both the nucleus and cytoplasm, where the protein acts as a transcriptional repressor and a modulator of its interacting proteins, respectively. DHPG (3,5-dihydroxyphenylglycine), a group I mGluR agonist, also up-regulated DREAM expression in cortical neurons. These results suggest that group I mGluR is the first identified receptor that may regulate DREAM activity in neurons.