title: P2Y receptors: focus on structural, pharmacological and functional aspects in the brain.
abstract: Purine and pyrimidine nucleotides have been identified as potent extracellular signalling molecules, acting at two classes of cell surface receptors, ionotropic P2X and metabotropic P2Y receptor (-R) types. Hitherto eight subtypes of the P2Y-R family have been cloned from mammalian species that exhibit sensitivity to the adenine nucleotides ATP/ADP (P2Y(1,11,12,13)), the uracil nucleotides UTP/UDP (P2Y(2,4,6) or UDP-glucose in the case of P2Y(14)) or both adenine and uracil nucleotides (P2Y(2)). The P2Y-Rs are G protein-coupled receptors activating phospholipase C via Galpha(q/11) protein and stimulating or inhibiting adenylyl cyclase via Galpha(s) and Galpha (i/o) proteins, respectively. These receptors may activate distinct signalling cascades. Although classical models predict that P2Y-Rs exist in the cell membrane as monomers, homo- or heterodimeric assemblies may be generated. Interactions with certain ion channels or ligand-gated receptors as well as the co-localization of several receptor subtypes in the same cell provide the basis for a high functional diversity. The proteins for various P2Y-Rs are expressed early in the embryonic brain and are broadly distributed on both, neurons and astroglial cells. P2Y-R involvement in the regulation of normal physiological processes on the cellular level or in vivo, such as modulation of transmitter release, generation of astroglial Ca(2+) waves, in diverse effects on behavioural functions and in the etiopathology of neurodegenerative diseases, are discussed and own data are presented. However, the exact understanding of the role of individual P2Y-R subtypes is still limited. Concerning the potentially important functions of P2Y-Rs, there is a strong need to develop stable, lipophilic and subtype-selective P2Y-R ligands, which may open new therapeutic strategies.
authors.affiliation: Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, D-04107 Leipzig, Germany. fisw@medizin.uni-leipzig.de
authors.forename: W
authors.initials: W
authors.lastname: Fischer
authors.forename: U
authors.initials: U
authors.lastname: Krügel
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008956:Models, Chemical; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction; D009435:Synaptic Transmission
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D002118:Calcium