P2 Receptors in Neurological and Cardiovascular Disorders
Figure 2
Structure and signaling functions of the P2 receptor. (a) Each functional P2 receptor is a trimer [18], with the three protein subunits arranged around a cation-permeable channel pore. The subunits all share a common topology, possessing two plasma membrane spanning domains (TM1 and TM2), a large extracellular loop with the ATP binding site, and containing 10 similarly spaced cysteines and glycosylation sites, and intracellular carboxyl and amino termini. (b) Brief ATP activation (10 seconds) of the P2 receptor results in rapid and reversible channel opening that is permeable to , , and . Acute receptor activation also triggers a series of cellular responses, such as depolarization, degranulation, and membrane blebbing, along with signaling cascades (see Figure 3 for further details). (c) Continued stimulation results in the formation of a larger plasma membrane pore, which facilitates the uptake of cationic molecules up to 900 Da (including ethidium bromide, which is frequently used as a tool to measure channel permeability, based on its property of generating a fluorescent signal upon DNA binding). Further activation of the receptor in some cell types results in the induction of apoptosis/cell lysis. ATP-induced increase in IL-1 release is mediated mainly through the activation of IL-1 converting enzyme (also known as caspase-1). Activation of the P2 receptor triggers the efflux of from cells which in turn activates IL-1 converting enzyme, leading to cleavage of pro-IL-1 to mature IL-1 and release from the cell.
