Related Experiment Video
Updated: Jul 11, 2026
07:36
Analysis of Raw and Processed Cyperi Rhizoma Samples Using Liquid Chromatography-Tandem Mass Spectrometry in Rats with Primary Dysmenorrhea
Published on: December 23, 2022
Membrane prostaglandin E synthase-1: a novel therapeutic target
Bengt Samuelsson1, Ralf Morgenstern, Per-Johan Jakobsson
1Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden. bengt.samuelsson@ki.se
Pharmacological Reviews
|September 20, 2007
Summary
Prostaglandin E2 (PGE2), a key molecule in the body, is produced by specific enzymes including mPGES-1. Targeting mPGES-1 shows promise for treating inflammatory diseases and other conditions.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Prostaglandin E2 (PGE2) is a crucial mediator with diverse biological functions, acting through EP1-4 receptors.
- PGE2 synthesis involves cyclooxygenase (COX) enzymes and subsequent conversion by PGE synthases, including cytosolic PGE synthase (cPGES) and membrane-bound mPGES-1 and mPGES-2.
- While cPGES and mPGES-2 are constitutive, mPGES-1 is primarily induced and utilizes COX-2-derived prostaglandin H2 (PGH2).
Purpose of the Study:
- To elucidate the role of mPGES-1 in PGE2 production and its implications in various physiological and pathological processes.
- To investigate the regulatory mechanisms of mPGES-1 expression, particularly its coordinate induction with COX-2 during inflammation.
- To assess the therapeutic potential of targeting mPGES-1 for disease treatment.
Main Methods:
- Analysis of mPGES-1 gene disruption in mouse models.
- Examination of mPGES-1 expression in response to inflammatory stimuli.
- Biochemical assays to determine enzyme kinetics and cofactor requirements (glutathione).
Main Results:
- mPGES-1 is a glutathione-dependent enzyme, upregulated by proinflammatory stimuli alongside COX-2.
- Glucocorticoids effectively reverse the coordinated upregulation of COX-2 and mPGES-1.
- Studies using mPGES-1 gene knockout mice highlight its critical role in female reproduction, inflammation, pain, fever, and tumorigenesis.
Conclusions:
- mPGES-1 is a key inducible enzyme in PGE2 biosynthesis, tightly regulated with COX-2.
- mPGES-1 plays significant roles in various pathological conditions, making it a promising therapeutic target.
- Inhibition of mPGES-1 offers a potential strategy for developing novel treatments for a range of diseases.
Related Concept Videos
01:20Drugs for Peptic Ulcer Disease: Prostaglandin Analogs as Mucosal Protective Agents
The gastric mucosa produces prostaglandins E2 (PGE2) and prostacyclin (PGI2), crucial in maintaining gastric health. They exert cytoprotective effects, including increasing bicarbonate secretion, releasing protective mucin, reducing gastric acid output, and preventing harmful vasoconstriction. These effects are mediated through various receptors, such as EP1, EP2, EP3, and EP4.
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
Non-steroidal anti-inflammatory drugs (NSAIDs) can induce peptic ulcers by inhibiting cyclooxygenase, decreasing...
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
Prostacyclin receptor agonists are a class of therapeutic agents integral to managing pulmonary arterial hypertension (PAH). These drugs operate by mimicking the action of prostaglandin I2, or PGI2, a naturally occurring compound in the body.
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:20Antiplatelet Drugs: Prostaglandin Synthesis, P2Y12 and Glycoprotein IIb/IIIa Inhibitors
Antiplatelet drugs emerge as frontline defenders against the insidious threat of thromboembolic diseases, where abnormal clots obstruct vital blood vessels. These drugs stand as bulwarks, inhibiting platelet aggregation and clot formation, thereby mitigating the risk of life-threatening conditions like myocardial infarction, coronary artery disease, and thrombotic strokes.
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
Prostaglandin synthesis inhibitors, exemplified by the widely known aspirin, wield their power by irreversibly acetylating...
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...
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...