Related Experiment Video
Updated: Jun 19, 2026
08:50
Prostaglandin Extraction and Analysis in Caenorhabditis elegans
Published on: June 25, 2013
Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity
Takayuki Kawano1, Josef Anrather, Ping Zhou
1Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
Nature Medicine
|January 25, 2006
Summary
Cyclooxygenase-2 (COX-2) drives neurotoxicity via EP1 receptors, which disrupt calcium balance. Inhibiting EP1 receptors protects the brain from stroke and excitotoxicity, offering a potential therapeutic strategy.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) is involved in neurotoxicity after hypoxia-ischemia.
- COX-2 inhibition shows therapeutic potential for ischemic stroke but carries cardiovascular risks.
Purpose of the Study:
- Identify downstream effectors of COX-2 neurotoxicity.
- Investigate the role of prostaglandin E(2) EP1 receptors in COX-2 mediated neurotoxicity.
Main Methods:
- Examined the role of EP1 receptors in neurotoxicity.
- Assessed the impact of EP1 receptor inhibition on brain injury models.
Main Results:
- Prostaglandin E(2) EP1 receptors are essential for COX-2 mediated neurotoxicity.
- EP1 receptors disrupt calcium homeostasis by impairing Na(+)-Ca(2+) exchange.
- EP1 receptor inhibition or gene inactivation ameliorates brain injury in various models, including middle cerebral artery (MCA) occlusion.
Conclusions:
- EP1 receptors augment calcium dysregulation, contributing to excitotoxic neuronal death.
- EP1 receptor inhibition is a promising therapeutic strategy for ischemic stroke, even when administered hours after occlusion.
More Related Videos
Related Concept Videos
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...
01:20Antiplatelet 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...
01:23Treatment 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...
01:20Drugs 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...
01:28Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists
Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy. SP binds and activates these...
01:17Gastritis-II: Pathophysiology
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...