PMID- 33259865
OWN - NLM
STAT- MEDLINE
DCOM- 20210114
LR  - 20210114
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 265
DP  - 2021 Jan 15
TI  - Possible mechanism and potential application of anti-opioid effect of 
      diazepam-binding inhibitor.
PG  - 118836
LID - S0024-3205(20)31589-7 [pii]
LID - 10.1016/j.lfs.2020.118836 [doi]
AB  - AIMS: Our previous study has demonstrated that porcine diazepam-binding inhibitor 
      (pDBI) and its active fragments, pDBI-16 and pDBI-19, have inhibition effect on 
      morphine analgesia in mice. The present study aimed to investigate the underlying 
      mechanism and potential application of this anti-opioid effect. MATERIALS AND 
      METHODS: Effect of DBI on morphine analgesia was examined by the tail electric 
      stimulation vocalization test. Complementary peptides and antiserum were used to 
      further confirm the effect of DBI in morphine tolerance and dependence. 
      Pharmacological and microinjection methods were used to investigate the 
      underlying mechanism. KEY FINDINGS: Firstly, pDBI administered either 
      intracerebroventricularly or intravenously dose-dependently inhibited morphine 
      analgesia, while blocking DBI-16 or DBI-19 by the complementary peptides for 
      DBI-16 (CP-DBI-16) or DBI-19 (CP-DBI-19) potentiated it in mice. Secondly, 
      explicit immunoexpression of DBI in the lateral habenular (LHb) was observed in 
      naive rats, and intra-LHb injection of pDBI dose-dependently abolished analgesic 
      effect produced by intra-periaqueductal gray (PAG) injection of morphine in rats. 
      Thirdly, pretreatment with N-Methyl-d-Aspartate receptor (NMDAR) antagonist 
      MK-801 or nitric oxide (NO) synthase inhibitor L-NAME abolished the inhibition 
      effect of pDBI, pDBI-16 or pDBI-19 on morphine analgesia in mice. Finally, 
      antiserum against DBI dose-dependently reversed analgesic tolerance induced by 
      increasing doses of morphine twice daily for 13 days in mice, while CP-DBI-16 or 
      CP-DBI-19 significantly inhibited naloxone-precipitated morphine withdrawal 
      jumping in mice. SIGNIFICANCE: Taken together, our results demonstrated that 
      NMDAR/NO signaling and LHb-PAG pathway are crucially involved in the anti-opioid 
      effect of DBI, which could provide a potential biological target for opioid 
      tolerance and dependence.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Qin, Wangjun
AU  - Qin W
AD  - Department of Pharmacy, China-Japan Friendship Hospital, Beijing 100029, China. 
      Electronic address: qwj2004wang@163.com.
FAU - Qu, Hong
AU  - Qu H
AD  - Center for Bioinformatics, State Key Laboratory of Protein and Plant Gene 
      Research, College of Life Sciences, Peking University, Beijing 100871, China.
FAU - Pan, Lin
AU  - Pan L
AD  - Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 
      100029, China.
FAU - Sun, Weiliang
AU  - Sun W
AD  - Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 
      100029, China.
FAU - Chen, Yuzhen
AU  - Chen Y
AD  - Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing 
      100029, China; State Key Laboratory of Membrane Biology, Peking University, 
      Beijing 100871, China. Electronic address: chenyuzhen2016pku@163.com.
FAU - Wu, Caihong
AU  - Wu C
AD  - State Key Laboratory of Membrane Biology, Peking University, Beijing 100871, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20201128
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Diazepam Binding Inhibitor)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/administration & dosage/*pharmacology
MH  - Animals
MH  - Diazepam Binding Inhibitor/administration & dosage/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Tolerance
MH  - Electric Stimulation
MH  - Male
MH  - Mice
MH  - Morphine/administration & dosage/*pharmacology
MH  - Naloxone/pharmacology
MH  - Narcotic Antagonists/administration & dosage/*pharmacology
MH  - Nitric Oxide/metabolism
MH  - Opioid-Related Disorders/drug therapy
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Swine
MH  - Tail
MH  - Vocalization, Animal/drug effects
OTO - NOTNLM
OT  - Anti-opioid
OT  - Diazepam-binding inhibitor
OT  - Lateral habenular
OT  - NMDA receptor
OT  - NO
EDAT- 2020/12/02 06:00
MHDA- 2021/01/15 06:00
CRDT- 2020/12/01 20:08
PHST- 2020/10/15 00:00 [received]
PHST- 2020/11/18 00:00 [revised]
PHST- 2020/11/20 00:00 [accepted]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/01/15 06:00 [medline]
PHST- 2020/12/01 20:08 [entrez]
AID - S0024-3205(20)31589-7 [pii]
AID - 10.1016/j.lfs.2020.118836 [doi]
PST - ppublish
SO  - Life Sci. 2021 Jan 15;265:118836. doi: 10.1016/j.lfs.2020.118836. Epub 2020 Nov 
      28.