Adenosine diphosphate receptor

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. 

Thienopyridines reduce platelet aggregation by inhibiting the activity of the adenosine diphosphate receptor. 

Clopidogrel is converted to an active thiol metabolite by several CYP isoforms, including 3A4 this then binds rapidly and irreversibly with platelet adenosine diphosphate receptors, thus inhibiting platelet aggregation, At present, inhibition of the antiplatelet effects of clopidogrel by atorvastatin represents a formulated but untested hypothesis, and these agents maybe administered concurrently. 

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). 

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... 

Mechanism of Action An aggregation inhibitor that inhibits the release of adenosine diphosphate from activated platelets, which prevents fibrinogen from binding to glycoprotein Ilb/IIIa receptors on the surface of activated platelets. TherapeuticEffect Inhibits platelet aggregation and thrombus formation. 

ADP (Adenosine diphosphate) 536 in adenylate system 302 - 304 complexes with metal ions 296 dissociation as acid 288 intracellular concentration 304 P-31 NMR spectrum 642 pka value of 293 in regulation 535 ADP-ribose (ADPR) 315, 778, 780 ADP-ribosylation 545, 778 ADP-ribosylation factors (ARFs) 559 Adrenaline (epinephrine) 534, 542, 553, 553s in adrenergic receptor 535 a-Adrenergic receptors 553, 558, 563 p-Adrenergic receptors 553, 554 in asthma 553 in heart failure 553 receptor kinase 553 structure (proposed) 534, 555 topology 555... 

Reeves JJ, Jones CA, Sheehan MJ, Vardey CJ, Whelan CJ (1997) Adenosine A3 receptors promote degranulation of rat mast cells both in vitro and in vivo. Inflamm Res 46(5) 180-184 Ribeiro JA, Walker J (1975) The effects of adenosine triphosphate and adenosine diphosphate on transmission at the rat and frog neuromuscular junctions. Br J Pharmacol 54(2) 213-218 Ribeiro JA, Sebastiao AM (1984) Enhancement of tetrodotoxin-induced axonal blockade by adenosine, adenosine analogues, dibutyryl cyclic AMP and methylxanthines in the frog sciatic nerve. Br J Pharmacol 83(2) 485—492... 

FIGURE 52.4 The insulin receptor. ATP = adenosine triphosphate ADP = adenosine diphosphate TYR = tyrosine. 

All interactions between UFH and platelets are complex and only partially elucidated, but it is known that heparin itself stimulates platelets via a platelet-binding domain of heparin (14). In the therapeutic range, UFH induces the release of P-selectin and activates GPIIb/llla receptors when adenosine diphosphate (ADP) or thrombin receptor agonist peptide stimulates platelet responsibility, and then enhances platelet aggregation (15,16). Even in healthy individuals, agonist-induced platelet aggregation is often enhanced when heparin is added. 

---