PMID- 30599218
OWN - NLM
STAT- MEDLINE
DCOM- 20200310
LR  - 20200310
IS  - 1873-2747 (Electronic)
IS  - 0361-9230 (Linking)
VI  - 146
DP  - 2019 Mar
TI  - The antinociceptive effects and molecular mechanisms of ghrelin(1-7)-NH(2) at the 
      supraspinal level in acute pain in mice.
PG  - 112-123
LID - S0361-9230(18)30544-6 [pii]
LID - 10.1016/j.brainresbull.2018.12.016 [doi]
AB  - Ghrelin(1-7)-NH(2) is the active N-terminal hepta-peptide of ghrelin as an 
      agonist at the ghrelin receptor GHS-R1alpha. The biological functions of 
      ghrelin(1-7)-NH(2) have not been well investigated. Therefore in this study, we 
      were interested in exploring the effects and molecular mechanisms of 
      ghrelin(1-7)-NH(2) in pain modulation at the supraspinal level using the tail 
      withdrawal test in mice. Intracerebroventricular (i.c.v.) injection of 
      ghrelin(1-7)-NH(2) (0.002, 0.02, 0.2 and 2 nmol/kg) induced a dose- and 
      time-related antinociceptive effect. This antinociceptive effect was fully 
      antagonized by co-injection with the GHS-R1alpha antagonist [D-Lys(3)]-GHRP-6, 
      indicating that this effect induced by ghrelin(1-7)-NH(2) was mediated through 
      the activation of GHS-R1alpha. Interestingly, naloxone, beta-funaltrexamine, 
      naloxonazine, and naltrindole, but not nor-binaltorphimine, could also antagonize 
      the antinociceptive effect markedly, suggesting that OPRM (primary mu(1) subtype) 
      and OPRD were involved in the antinociceptive response induced by 
      ghrelin(1-7)-NH(2). Furthermore, the qRT-PCR and Western blot results indicated 
      that both mRNA and protein levels of PENK and OPRD were up-regulated 
      significantly. Using the fluorescence labeling method, our results showed that 
      ghrelin(1-7)-NH(2) (i.c.v.) was mainly distributed at the dorsal 3rd ventricle 
      and hippocampus where there are regions with high expressions of ghrelin, GHS-R1alpha 
      and ORs. All these results indicated that ghrelin(1-7)-NH(2) initially activated 
      the GHS-R1alpha, then activated the OPRM, as well as increased the release of 
      endogenous PENK to activate of OPRD to produce antinociception. These results 
      contributed to understanding the mechanisms of antinociception induced by 
      ghrelin(1-7)-NH(2). Furthermore, ghrelin(1-7)-NH(2) as the active fragment of 
      ghrelin may be a promising peptide for developing new analgesic drugs.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Wu, Bing
AU  - Wu B
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Liu, Yongling
AU  - Liu Y
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Liu, Fuyan
AU  - Liu F
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China; Department of Anatomy, Basic Medical Teaching 
      and Research Section of Nanchang Health School, Nanchang, Jiangxi, 330006, China.
FAU - Deng, Qing
AU  - Deng Q
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Wang, Jinglei
AU  - Wang J
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Han, Renwen
AU  - Han R
AD  - Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, 
      330008, China.
FAU - Zhang, Dalei
AU  - Zhang D
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Chen, Jiaxiang
AU  - Chen J
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China.
FAU - Wei, Jie
AU  - Wei J
AD  - Department of Physiology, Medical College of Nanchang University, Bayi Road 461, 
      Nanchang, Jiangxi, 330006, China. Electronic address: jwei@ncu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181229
PL  - United States
TA  - Brain Res Bull
JT  - Brain research bulletin
JID - 7605818
RN  - 0 (Analgesics)
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Ghrelin)
RN  - 0 (Ghsr1a protein, mouse)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Oligopeptides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Ghrelin)
RN  - 0 (Receptors, Opioid)
RN  - 4H7N4I6X6A (growth hormone releasing hexapeptide)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics/administration & dosage
MH  - Analgesics, Opioid/pharmacology
MH  - Animals
MH  - Ghrelin/*administration & dosage
MH  - Injections, Intraventricular
MH  - Male
MH  - Mice
MH  - Morphine
MH  - Narcotic Antagonists/administration & dosage
MH  - Oligopeptides/administration & dosage
MH  - Pain/*drug therapy
MH  - Peptide Fragments/administration & dosage
MH  - Receptors, Ghrelin/agonists/metabolism
MH  - Receptors, Opioid/drug effects
OTO - NOTNLM
OT  - Antinociception
OT  - Distribution
OT  - GHS-R1alpha
OT  - Ghrelin(1-7)-NH(2)
OT  - Opioid receptors
EDAT- 2019/01/02 06:00
MHDA- 2020/03/11 06:00
CRDT- 2019/01/02 06:00
PHST- 2018/07/16 00:00 [received]
PHST- 2018/12/07 00:00 [revised]
PHST- 2018/12/26 00:00 [accepted]
PHST- 2019/01/02 06:00 [pubmed]
PHST- 2020/03/11 06:00 [medline]
PHST- 2019/01/02 06:00 [entrez]
AID - S0361-9230(18)30544-6 [pii]
AID - 10.1016/j.brainresbull.2018.12.016 [doi]
PST - ppublish
SO  - Brain Res Bull. 2019 Mar;146:112-123. doi: 10.1016/j.brainresbull.2018.12.016. 
      Epub 2018 Dec 29.