Overview of the P2 receptors.
The release of nucleotides in extracellular fluids can result from cell necrosis, exocytosis of secretory granules (such as platelet dense granules), or efflux through membrane channels. In addition, recent evidence suggests that vesicular trafficking is an important pathway of nucleotide release. Once in the extracellular fluids, they are rapidly degraded by ectonucleotidases, such as CD39, that play a key role in neutralizing the platelet aggregatory action of adenosine diphosphate (ADP), and act on two families of receptors: the ionotropic P2X receptors and the G-protein-coupled P2Y receptors. The family of P2X receptors encompasses seven genes. Currently, there are eight genuine P2Y receptors that can be subdivided into two structurally distinct subfamilies. Whereas P2X receptors are receptors of ATP, the different P2Y receptors are activated by distinct nucleotides, diphosphates or triphosphates, or purines or pyrimidines, some of them being conjugated to sugars. The study of knockout mice has demonstrated that P2X receptors play important roles in the neurogenic control of smooth muscle contraction, in pain and visceral perception, and in macrophage functions. The phenotype of P2Y null mice so far is more restricted: inhibition of platelet aggregation to ADP and increased bleeding time in P2Y (1)(-/-) and P2Y (12)(-/-) mice and lack of epithelial responsiveness to nucleotides in airways (P2Y (2)(-/-)) and intestine (P2Y (4)(0/-)).
Boeynaems
Jean-Marie
JM
Institute of Interdisciplinary Research, School of Medicine and Institute of Molecular and Medical Biology, Brussels, Belgium. jmboeyna@ulb.ac.be
Communi
Didier
D
Gonzalez
Nathalie Suarez
NS
Robaye
Bernard
B
D000244:Adenosine Diphosphate / Q000502:physiology; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D005089:Exocytosis; D045604:Extracellular Fluid / Q000378:metabolism; D006410:Hematopoiesis / Q000502:physiology; D006474:Hemorrhagic Disorders / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D010641:Phenotype; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000737:chemistry / Q000145:classification / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002712:Chlorides; D043562:Receptors, G-Protein-Coupled; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate