Related Experiment Video
Updated: Jun 14, 2026
09:13
Turbidimetry on Human Washed Platelets: The Effect of the Pannexin1-inhibitor Brilliant Blue FCF on Collagen-induced Aggregation
Published on: April 6, 2017
Regulation of PAF-induced platelet responses by cyclic nucleotides
R E Catalán1, A M Martínez, M D Aragonés
1Departamento de Biología Molecular, Centra de Biología Molecular 'Severo Ochoa' (CSIC-UAM), Universidad Autónoma de Madrid, E-28049, Madrid, Spain.
Platelets
|March 20, 2010
Summary
Platelet activation involves cross-talk between cyclic nucleotides and signaling pathways. Cyclic AMP and cyclic GMP modulate Platelet-Activating Factor (PAF)-induced protein phosphorylation, impacting platelet function.
Area of Science:
- Biochemistry
- Cell Signaling
- Platelet Physiology
Background:
- Platelet activation is a complex process involving various signal transduction pathways.
- Cyclic nucleotides, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), are known regulators of platelet function.
- Platelet-Activating Factor (PAF) is a potent activator of platelets, triggering multiple downstream signaling events.
Purpose of the Study:
- To investigate the cross-talk mechanisms between the cyclic nucleotide system and other transduction systems in PAF-activated platelets.
- To elucidate the role of cAMP and cGMP in modulating PAF-induced protein phosphorylation.
- To examine the relationship between pp47 phosphorylation and serotonin secretion in platelets.
Main Methods:
- Stimulation of platelets with PAF, cAMP-elevating agents (e.g., forskolin), and cGMP-elevating agents (e.g., sodium nitroprusside).
- Analysis of protein phosphorylation, specifically tyrosine phosphorylation of pp 125(FAK) and serine/threonine phosphorylation of pp47.
- Measurement of serotonin secretion from platelets.
Main Results:
- PAF induced time- and concentration-dependent tyrosine phosphorylation of pp 125(FAK).
- Both cAMP and cGMP elevated agents inhibited PAF-induced pp 125(FAK) tyrosine phosphorylation.
- cAMP, but not cGMP, inhibited PAF-induced pp47 serine/threonine phosphorylation; cGMP synergistically enhanced forskolin's inhibitory effect on pp47 phosphorylation.
- pp47 phosphorylation was not closely correlated with serotonin secretion.
- Sodium nitroprusside inhibited serotonin secretion independently and synergistically with forskolin, without affecting pp47 phosphorylation.
Conclusions:
- Distinct cross-talk mechanisms exist between cyclic nucleotide signaling and PAF-induced pathways in platelets.
- cAMP and cGMP differentially regulate specific protein phosphorylation events downstream of PAF.
- Serotonin secretion is regulated independently of pp47 phosphorylation, with both cGMP and cAMP pathways contributing to its inhibition.
Related Concept Videos
01:22Formation of the Platelet Plug
The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
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...
01:18Structure and Function of Platelets
The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000 platelets, with...
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...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...