Adenosine triphosphate, ATP
Adenosine triphosphate, ATP, is, in addition to its role of energy reserve of the cell and component of the nucleic acids, a purinergic transmitter which is used in the same indications as adenosine.
ATP is synthesized during glycolysis, but especially during mitochondrial respiration, from ADP or adenosine diphosphate, thanks to ATPase of type F or ATP synthase. The ADP comes from the adenosine monophosphate or AMP.
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Metabolism of ATP
Mainly intracellular, it is released by exocytosis into the synaptic space at the same time as other transmitters like catecholamines. It is also released during cellular damage and hypoxia.
Intracellular ATP is the most important source of cellular energy which is liberated during its transformation into ADP. ATP is a donor of phosphate groups for phosphorylations. Increase of intracellular ATP levels in pancreatic beta cells induces closure of plasma membrane potassium channels, depolarization, calcium penetration and insulin release. There are also potassium channels controlled by ATP in mitochondria.
Extracellular ATP activates cell-surface receptors of P2 type, divided in two sub-groups called transmitter-gated ion channel P2X receptors, permeable in the open state to sodium, potassium and calcium and metabotropropic P2Y receptors coupled to G proteins.
The extracellular effects of the ATP are difficult to systematize: it induces nitric oxide release by endothelial cells, opening of cardiac potassium channels leading to hyperpolarisation and it increases intracytoplasmic calcium in cells such as macrophages. In the central nervous system, the receptors channels of type P2X, when they are activated by ATP, let calcium and sodium enter neurons and play a part in synaptic transmission. The activation of P2X2 and P2X3 receptors elicits pain, nociception, and the antagonists of these receptors have antalgic effects. Under certain pathological conditions, they could have a toxic role similar to that of glutamate via NMDA receptors.
ATP is quickly hydrolyzed by nucleotidases present on the surface of various types of cells to give successively ADP, AMP and adenosine.
ATP is used in the treatment of paroxystic supraventricular tachycardia but, as it does not penetrate into cells, its administration, even by parenteral route, does not make it possible to correct an intracellular deficiency.
ADP, adenosine diphosphate, is a powerful platelet aggregating molecule which acts by activating platelet surface membrane receptors called P2Y12. Ticlopidine and clopidrogrel (and products being studied such as prasugrel) are inhibitors of this receptor. See Coagulation.
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