P2X receptors are a family of seven (P2X1R-P2X7R) cation permeable ligand-gated ion channels (LGICs) that open in response to binding by the extracellular ligand, ATP. P2X receptors have a high permeability to Ca2+, Na+, and K+. Moreover, P2X receptors show widely expressed in excitatory and non-excitatory cells. P2X receptors have a widespread tissue distribution. On some smooth muscle cells, P2X receptors mediate the fast excitatory junction potential that leads to depolarization and contraction. There is some degree of subtype specificity as to which P2X receptor subtypes are expressed on specific cell types, with P2X1 receptors being particularly prominent in smooth muscle cells, and P2X2 being widespread throughout the autonomic nervous system.
PPADS is a non-selective P2X receptor antagonist, blocks recombinant P2X1, P2X2, P2X3, P2X5. Meanwhile, PPADS also inhibits native P2Y2-like and recombinant P2Y4 receptors. In studies on native smooth muscle preparations that express functional P2X1Rs, PPADS shows P2XR antagonism for the first time. Subsequently PPADS displays effective at other native and recombinant P2XRs. Lys-249 in the extracellular domain of P2XR contributes to the role of PPADS. Moreover, PPADS induces a conformational change at the cysteine-rich head (CRH) region adjacent to the orthosteric ATP-binding pocket. Besides, PPADS is an inhibitor of the reverse mode of the Na/Ca2+ exchanger in guinea pig airway smooth muscle. PPADS inhibits Na/Ca2+ exchanger in a time- and concentration-dependent manner. Moreover, PPADS does not affect L-type Ca2+ channels, and shows more specific than KB-R7943.
To sum up, PPADS is a non-selective P2X receptor antagonist, blocks recombinant P2X1, P2X2, P2X3, P2X5, native P2Y2-like, and recombinant P2Y4 receptors.
 Edgar Flores-Soto, et al. Eur J Pharmacol. 2012 Jan 15;674(2-3):439-44.
 Hong Huo, et al. J Biol Chem. 2018 Aug 17;293(33):12820-12831.