Related Experiment Video
Updated: Aug 10, 2026
07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Endomorphins fully activate a cloned human mu opioid receptor
1Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, OH 45267-0521, USA.
FEBS Letters
|December 16, 1998
Summary
Endomorphins are potent full agonists that activate human mu opioid receptors. They effectively inhibit cAMP pathways and activate potassium channels, similar to DAMGO.
Area of Science:
- Pharmacology
- Neuroscience
- Molecular Biology
Background:
- Endomorphins are newly discovered endogenous ligands.
- They show high selectivity for mu opioid receptors.
Purpose of the Study:
- To characterize endomorphin binding and functional activation of the cloned human mu opioid receptor.
- To investigate the downstream signaling pathways modulated by endomorphins.
Main Methods:
- Radioligand binding assays to assess receptor selectivity.
- Forskolin-stimulated cAMP inhibition assays.
- Xenopus oocyte expression system to study G-protein-activated inwardly rectifying potassium (GIRK) channels.
Main Results:
- Endomorphin-1 and endomorphin-2 demonstrated high binding selectivity for mu opioid receptors over delta and kappa opioid receptors.
- Both endomorphins dose-dependently inhibited forskolin-stimulated cAMP increase.
- Application of endomorphins activated GIRK channels in a dose-dependent manner, an effect blocked by naloxone.
- Endomorphins functioned as full agonists with efficacy comparable to DAMGO.
Conclusions:
- Endomorphins act as full agonists at the human mu opioid receptor.
- They effectively inhibit the cAMP/adenylyl cyclase pathway.
- They activate G-protein-activated inwardly rectifying potassium (GIRK) channels.
More Related Videos
07:48Tracking Drug-induced Changes in Receptor Post-internalization Trafficking by Colocalizational Analysis
Published on: July 3, 2015
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
01:20Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
01:15Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:25Cholinergic Receptors: Muscarinic
The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine.
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...
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...