The impact of multifunctional enkephalin analogs and morphine on the protein changes in crude membrane fractions isolated from the rat brain cortex and hippocampus
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F24%3A00583343" target="_blank" >RIV/67985823:_____/24:00583343 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1016/j.peptides.2024.171165" target="_blank" >https://doi.org/10.1016/j.peptides.2024.171165</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.peptides.2024.171165" target="_blank" >10.1016/j.peptides.2024.171165</a>
Alternative languages
Result language
angličtina
Original language name
The impact of multifunctional enkephalin analogs and morphine on the protein changes in crude membrane fractions isolated from the rat brain cortex and hippocampus
Original language description
Endogenous opioid peptides serve as potent analgesics through the opioid receptor (OR) activation. However, they often suffer from poor metabolic stability, low lipophilicity, and low blood-brain barrier permeability. Researchers have developed many strategies to overcome the drawbacks of current pain medications and unwanted biological effects produced by the interaction with opioid receptors. Here, we tested multifunctional enkephalin analogs LYS739 (MOR/DOR agonist and KOR partial antagonist) and LYS744 (MOR/DOR agonist and KOR full antagonist) under in vivo conditions in comparison with MOR agonist, morphine. We applied 2D electrophoretic resolution to investigate differences in proteome profiles of crude membrane (CM) fractions isolated from the rat brain cortex and hippocampus exposed to the drugs (10 mg/kg, seven days). Our results have shown that treatment with analog LYS739 induced the most protein changes in cortical and hippocampal samples. The identified proteins were mainly associated with energy metabolism, cell shape and movement, apoptosis, protein folding, regulation of redox homeostasis, and signal transduction. Among these, the isoform of mitochondrial ATP synthase subunit beta (ATP5F1B) was the only protein upregulation in the hippocampus but not in the brain cortex. Contrarily, the administration of analog LYS744 caused a small number of protein alterations in both brain parts. Our results indicate that the KOR full antagonism, together with MOR/DOR agonism of multifunctional opioid ligands, can be beneficial in treating chronic pain states by reducing changes in protein expression levels but retaining analgesic efficacy.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
<a href="/en/project/LTAUSA18110" target="_blank" >LTAUSA18110: Selection of diagnostic markers of the long-term effect of multifunctional peptide agonists and antagonists targeting µ-, δ- and κ-opioid receptors – search for new possibilities for treatment of chronic pain.</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Peptides
ISSN
0196-9781
e-ISSN
1873-5169
Volume of the periodical
174
Issue of the periodical within the volume
April
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
171165
UT code for WoS article
001183530600001
EID of the result in the Scopus database
2-s2.0-85183979619