Let-7 microRNAs and Opioid Tolerance.
1Department of Biopharmaceutical Sciences, Cancer Center, University of Illinois Chicago, IL, USA.
Frontiers in Genetics
|June 28, 2012
Summary
MicroRNAs (miRs) regulate opioid receptors, impacting pain relief and tolerance. The let-7 family of miRs is key in modulating μ opioid receptor (MOR) function and opioid tolerance development.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Opioid analgesics, like morphine, treat pain but chronic use leads to tolerance.
- The μ opioid receptor (MOR) mediates analgesia and tolerance.
- MicroRNAs (miRs) are small non-coding RNAs regulating gene expression post-transcriptionally.
Purpose of the Study:
- To explore the role of miRs in regulating opioid receptor actions.
- To understand how miRs influence opioid tolerance.
- To review the interaction between miRs and MOR in opioid tolerance.
Main Methods:
- Review of existing literature on opioid receptors, miRs, and opioid tolerance.
- Focus on the post-transcriptional regulation of MOR mRNA by miRs.
- Examination of the let-7 family of miRs in MOR function.
Main Results:
- The 3'-untranslated region (3'-UTR) of MOR mRNA is critical for post-transcriptional regulation.
- miRs bind to the 3'-UTR of target mRNAs, decreasing protein formation.
- The let-7 family of miRs significantly regulates MOR function and opioid tolerance.
Conclusions:
- miRs represent a crucial layer of post-transcriptional gene regulation in the nervous system.
- miRs, particularly the let-7 family, play a significant role in modulating opioid receptor activity.
- Understanding miR-MOR interactions offers insights into managing opioid tolerance.
More Related Videos
07:23Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
16:02Demonstration of the Sequence Alignment to Predict Across Species Susceptibility Tool for Rapid Assessment of Protein Conservation
Published on: February 10, 2023
Related Concept Videos
01:25Analgesia and Pain Management
Pain is critical to various clinical pathologies, provoking an urgent need for effective management. Pain, whether acute or chronic, is a complex neurochemical process. Its alleviation depends on the type, with nonopioid analgesics effective for mild to moderate pain, such as musculoskeletal or inflammatory pain, while neuropathic pain responds best to anticonvulsants, tricyclic antidepressants, or serotonin/norepinephrine reuptake inhibitors. For severe acute or chronic pain, opioids may be...
01:22Opioid Receptors: Overview
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2, D-Pen5]-enkephalin or DPDPE for...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
01:15Opioid Analgesics: Synthetic and Semisynthetic Opioids
Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
01:20Opioid Analgesics: Morphine and Other Natural Cogeners
Opioids are a class of drugs that mimic endogenous opioid peptides and act on opioid receptors, and help in pain relief. These compounds are classified as natural, synthetic, or semi-synthetic. Natural opioids, like morphine, codeine, and thebaine, are derived from the opium poppy plant (Papaver somniferum or Papaver album) and are termed opiates. Synthetic opioids are artificial, while semi-synthetic opioids combine natural and synthetic compounds. Morphine, a prototypical opioid, possesses a...