Regulation of Opioid Receptors by Their Endogenous Opioid Peptides.
Dynorphins
Endorphins
Enkephalins
GPCR
Opioid receptors
Journal
Cellular and molecular neurobiology
ISSN: 1573-6830
Titre abrégé: Cell Mol Neurobiol
Pays: United States
ID NLM: 8200709
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
02
07
2020
accepted:
18
11
2020
pubmed:
4
1
2021
medline:
15
12
2021
entrez:
3
1
2021
Statut:
ppublish
Résumé
Activation of μ, δ, and κ opioid receptors by endogenous opioid peptides leads to the regulation of many emotional and physiological responses. The three major endogenous opioid peptides, β-endorphin, enkephalins, and dynorphins result from the processing of three main precursors: proopiomelanocortin, proenkephalin, and prodynorphin. Using a knockout approach, we sought to determine whether the absence of endogenous opioid peptides would affect the expression or activity of opioid receptors in mice lacking either proenkephalin, β-endorphin, or both. Since gene knockout can lead to changes in the levels of peptides generated from related precursors by compensatory mechanisms, we directly measured the levels of Leu-enkephalin and dynorphin-derived peptides in the brain of animals lacking proenkephalin, β-endorphin, or both. We find that whereas the levels of dynorphin-derived peptides were relatively unaltered, the levels of Leu-enkephalin were substantially decreased compared to wild-type mice suggesting that preproenkephalin is the major source of Leu-enkephalin. This data also suggests that the lack of β-endorphin and/or proenkephalin does not lead to a compensatory change in prodynorphin processing. Next, we examined the effect of loss of the endogenous peptides on the regulation of opioid receptor levels and activity in specific regions of the brain. We also compared the receptor levels and activity in males and females and show that the lack of β-endorphin and/or proenkephalin leads to differential modulation of the three opioid receptors in a region- and gender-specific manner. These results suggest that endogenous opioid peptides are important modulators of the expression and activity of opioid receptors in the brain.
Identifiants
pubmed: 33389463
doi: 10.1007/s10571-020-01015-w
pii: 10.1007/s10571-020-01015-w
pmc: PMC8277103
mid: NIHMS1659492
doi:
Substances chimiques
Analgesics, Opioid
0
Opioid Peptides
0
Receptors, Opioid
0
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
100929-53-1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1103-1118Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK066604
Pays : United States
Organisme : NIDA NIH HHS
ID : R37 DA008863
Pays : United States
Organisme : NIH HHS
ID : DA008863
Pays : United States
Organisme : NIH HHS
ID : NS026880
Pays : United States
Organisme : National Institutes of Health (US)
ID : DA08622
Organisme : NINDS NIH HHS
ID : R01 NS026880
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK066604
Pays : United States
Organisme : National Institutes of Health (US)
ID : DK066604
Organisme : NIDDK NIH HHS
ID : R01 DK068400
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA008863
Pays : United States
Organisme : NIDA NIH HHS
ID : R56 DA008863
Pays : United States
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