Platelet activation receptors

The authors have coHsdxrrated for many years in studies on platelet activating receptors, including not only receptors for a-thrombin but also those for collagen (CD36 and GPVI, laminin (67kOA), and adenosine diphosphate. 

The formation of a platelet aggregate requires the recruitment of additional platelets from the blood stream to the injured vessel wall. This process is executed through a variety of diffusible mediators which act through G-protein-coupled receptors. The main mediators involved in this process are adenosine diphosphate (ADP), thromboxane A2 (TXA2), and thrombin (factor Ila). These mediators of the second phase of platelet activation are formed in different ways. While ADP is secreted from platelets by exocytosis, the release of TXA2 follows its new formation in activated platelets. Thrombin can be formed on the surface of activated platelets (see Fig. 2). 

Collagen is a major component of connective tissue that becomes exposed at the subendothelium of injured blood vessels. It contributes to platelet adhesion and also plays a role in platelet activation by binding to several receptors on platelets such as integrin a 2(3 1 or glycoprotein VI (GP VI). 

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Platelet-activating Factor Platelet Aggregation Inhibitors Platelet-derived Growth Factor Receptor Platelet Inhibitors Platelets... 

These cells respond to a number of different chemoattractants which have specific and distinct receptors on the membrane surface (for recent reviews see Refs. 3 and 4). Such chemoattractants include N-formylpeptides, which are bacterial peptides, and mediators of inflammation such as leukotriene B4, C5a, and platelet activating factor. 

Clemetson KJ Platelet activation signal transduction via membrane receptors. Thromb Haemost 1995 74 111. 

The mechanisms involved in platelet activation are discussed in Chapter 51 (see Figure 51-8). The process involves interaction of the stimulus (eg, thrombin) with a receptor, activation of G proteins, stimulation of phospholipase C, and hberation from phosphatidylinositol... 

Ticlopidine inhibits the P2Yj2 platelet ADP receptor, thus inhibiting ADP-dependent activation of the GP Ilb/IIIa receptor. It has a slow onset of action and takes 3-7 days to reach its maximal antiplatelet effect. It is inactive in vitro and must undergo activation by the hepatic cytochrome p450 enzyme system. Secondary prevention trials have found that ticlopidine-treated patients have an estimated RRR of 33% for the composite endpoint of stroke, myocardial infarction, or vascular death after ischemic stroke. Significant adverse effects include bone marrow depression, rash, diarrhea, and thrombotic thrombocytopenic purpura. No clinical trials have studied ticlopidine for the treatment of stroke in the acute phase. 

Administration of clopidogrel is recommended for all patients with STE ACS (Table 5—2).3 Clopidogrel blocks adenosine diphosphate receptors on platelets, preventing the expression of glycoprotein Ilb/IIIa receptors and thus platelet activation and aggregation. 

Cundell, D.R., Gerard, N.P., Gerard, C., Idanpaan-Heikkila, I. and Tuomanen, E.I. (1995) Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 377, 435-438. 

Bito, H., Nakamura, M., Honda, Z. etal. Platelet-activating factor (PAF) receptor in rat brain PAF mobilizes intracellular Ca2+ in hippocampal neurons. Neuron 9 285-294, 1992. 

PAF platelet-activating factor PTBR peripheral-type benzodiazepine receptor... 

A partially or completely occlusive clot forms on top of the raptured plaque. Exposure of collagen and tissue factor induce platelet adhesion and activation, which promote release of adenosine diphosphate and thromboxane A2 from platelets. These produce vasoconstriction and potentiate platelet activation. A change in the conformation of the glycoprotein (GP) Ilb/IIIa surface receptors of platelets occurs that cross-links platelets to each... 

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