LAUSR

The ionotropic P2X3 receptor (P2X3R) subtype is one of the seven mammalian P2X1-7 receptor belonging to the P2 purinergic receptor family together with the metabotropic P2Y1-2, 4-6,11-14 ones (Fredholm et al., 2011). As the other P2X ion channels, it is a trimeric cell surface receptor permeable to Na, K, and Ca cations and it is activated by the natural ligand adenosine-5′-triphosphate (ATP, 1, Figure 1). Each subunit is constituted by two trans-membrane domains connected by a large glycosylated extracellular loop, which contains many disulfide bonds and the ATP binding site (Browne et al., 2010). P2X3Rs are assembled as homotrimers, constituted by three subunits of P2X3Rs, or heterotrimers, constituted by two P2X3Rs and one P2X2R subunits (P2X2/3Rs) (Lewis et al., 1995). A difference between the two forms is represented by their fast or slow desensitization after prolonged exposure to agonists; hence P2X3Rs undergo rapid inactivation/desensitization during exposure to ATP or to the selective agonist α,β-methyleneATP (α,β-meATP, 2, Figure 1), which is accelerated by increasing the agonist dose, while P2X2/3Rs shows either mixed (twocomponent) or slow-type desensitization (Giniatullin and Nistri, 2013).