The active fragments of ghrelin cross the blood–brain barrier and enter the brain to produce antinociceptive effects after systemic administration

G (1-5)-NH 2 , G (1-7)-NH 2 , and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. T...

Full description

Saved in:
Bibliographic Details
Published in:Canadian journal of physiology and pharmacology 2021-10, Vol.99 (10), p.1057-1068
Main Authors: Fan, Bao-wei, Liu, Yong-ling, Zhu, Gui-xian, Wu, Bing, Zhang, Min-min, Deng, Qing, Wang, Jing-lei, Chen, Jia-xiang, Han, Ren-wen, Wei, Jie
Format: Article
Language:English
Subjects:
Acute Pain - drug therapy
Acute Pain - etiology
Acute Pain - metabolism
Acute Pain - pathology
Analgesics - pharmacology
Animals
Animals, Outbred Strains
antinociception
barrière hémo-encéphalique
Blood-brain barrier
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
Brain - drug effects
Brain - metabolism
Ghrelin
Ghrelin - administration & dosage
Ghrelin - pharmacokinetics
Ghrelin - pharmacology
GHS-R1α
Hot Temperature - adverse effects
Injection
Intravenous administration
Male
Mice
Naloxone
Narcotic Antagonists - pharmacology
Narcotics
Neuroimaging
Opioid receptors
Pain perception
Physiological aspects
Receptors, Ghrelin - antagonists & inhibitors
Receptors, Ghrelin - metabolism
Receptors, Opioid - chemistry
Receptors, Opioid - metabolism
récepteurs opioïdes
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:G (1-5)-NH 2 , G (1-7)-NH 2 , and G (1-9) are the active fragments of ghrelin. The aim of this study was to investigate the antinociceptive effects, their ability to cross the blood–brain barrier, and the receptor mechanism(s) of these fragments using the tail withdrawal test in male Kunming mice. The antinociceptive effects of these fragments (2, 6, 20, and 60 nmol/mouse) were tested at 5, 10, 20, 30, 40, 50, and 60 min after intravenous (i.v.) injection. These fragments induced dose- and time-related antinociceptive effects relative to saline. Using the near infrared fluorescence imaging experiments, our results showed that these fragments could cross the brain–blood barrier and enter the brain. The antinociceptive effects of these fragments were completely antagonized by naloxone (intracerebroventricular, i.c.v.); however, naloxone methiodide (intraperitoneal, i.p.), which is the peripheral restricted opioid receptor antagonist, did not antagonize these antinociceptive effects. Furthermore, the GHS-R1α antagonist [D-Lys 3 ]-GHRP-6 (i.c.v.) completely antagonized these antinociceptive effects, too. These results suggested that these fragments induced antinociceptive effects through central opioid receptors and GHS-R1α. In conclusion, our studies indicated that these active fragments of ghrelin could cross the brain–blood barrier and enter the brain and induce antinociceptive effects through central opioid receptors and GHS-R1α after intravenous injection.
ISSN:0008-4212
1205-7541
DOI:10.1139/cjpp-2020-0668