Interaction of P2 purinergic receptors with cellular macromolecules.
Ionotropic P2X and metabotropic P2Y receptors interact with a number of macromolecules in the cell membrane which may contribute to their functional plasticity. P2X receptors are homomeric or heteromeric assemblies of three subunits. P2Y receptors may form oligomeric complexes either with the same or with other P2Y receptor types. Although the signalling mechanism of P2X receptor channels is fast (within milliseconds) and relatively simple, by originating from the opening of an ion channel permeable to mono- and divalent cations, various macromolecules may modify the trafficking of these receptors to and from the cell membrane, as well as their activation and desensitization kinetics, and the possible opening of membrane pores induced by long-lasting exposure to agonists. P2X and Cys-loop receptors may physically interact with each other, resulting in mutual current occlusion. Heteromeric P2Y receptors may, via G(s), G(q/11) or G(i/o) protein-coupling and activation of the respective transduction mechanisms, mediate responses in the range of a few seconds. However, P2Y receptors may also interact with the signalling cascade of, e.g. receptor tyrosine kinases, and thereby mediate responses on a much slower time scale (within hours to days). In addition, P2Y receptors may interact with small, homomeric G proteins, integrins, and PDZ proteins. Eventually, P2Y receptors may cross-talk via Galpha-dependent signalling with other G protein-coupled receptors and via Gbetagamma (or indirectly Galpha)-dependent signalling with various ion channels. Thus, the activation of P2X and P2Y receptors by extracellular adenosine triphosphate/adenosine diphosphate or uridine triphosphate/uridine diphosphate may trigger specific chains of events which interact at the level of the individual elements both with each other and with the transduction mechanisms of other receptors, creating a huge diversity of the possible effects.
Köles
Laszlo
L
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Haertelstrasse 16-18, 04107 Leipzig, Germany.
Gerevich
Zoltan
Z
Oliveira
João Felipe
JF
Zadori
Zoltan Sandor
ZS
Wirkner
Kerstin
K
Illes
Peter
P
D000818:Animals; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D046911:Macromolecular Substances / Q000378:metabolism*; D020239:Receptor Cross-Talk; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015398:Signal Transduction
D007473:Ion Channels; D046911:Macromolecular Substances; D018048:Receptors, Purinergic P2