Regulation of Opioid Receptors by Their Endogenous Opioid Peptides
| Autor: | Lakshmi A. Devi, John E. Pintar, Dinah L. Ramos-Ortolaza, Hui Pan, Malcom J. Low, Ivone Gomes, Michael D. Hayward, Achla Gupta, Srinivas Gullapalli |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty medicine.drug_class Dynorphin Article Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Opioid receptor Internal medicine medicine Animals Endorphins Opioid peptide Receptor G protein-coupled receptor Mice Knockout Chemistry Brain Cell Biology General Medicine Enkephalin Ala(2)-MePhe(4)-Gly(5) Proenkephalin Analgesics Opioid Mice Inbred C57BL 030104 developmental biology Endocrinology Opioid Peptides Opioid Receptors Opioid Female hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cell Mol Neurobiol |
| ISSN: | 1573-6830 0272-4340 |
| DOI: | 10.1007/s10571-020-01015-w |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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