Table 2. Effects of P2 receptor antagonism/agonism on ARPKD and ADPKD development.
| Target | ADPKD or ARPKD | Species/model | Antagonist | Agonist | Action (effect) | Reference |
|---|---|---|---|---|---|---|
| Ionotropic P2X receptors | ||||||
| P2Xs | ADPKD | Human ADPKD epithelial primary cultures/in vitro | ATP αβmeATP bzATP |
Increased cytoplasmic [Ca2+]i, stimulated secretory Cl− transport | [140] | |
| MDCK-derived cysts (ADPKD)/in vitro | PPADS; Suramin (non-selective P2 receptor antagonist); Reactive blue2; Apyrase (ATP scavenger) |
bzATP | Reduced cyst growth and slowed disease progression | [141] | ||
| MDCK-derived cysts (ADPKD)/in vitro | Suramin Apyrase |
Reduced ATP-mediated fluid secretion and cyst development | [142] | |||
| P2X4 | ARPKD | PCK rat (ARPKD model)/in vivo | isoPPADS (non-selective P2X antagonist); 5-BDBD (P2X4) |
αβmeATP | Regulated [Ca2+]i | [63] |
| cpk/cpk ARPKD mice/in vitro | oxidized ATP (oxATP) | bzATP (P2X7); ATP; UTP |
bzATP reduced cyst development; oxATP abrogated this effect ATP, UTP had lesser effects than bzATP | [143] | ||
| PCK rat (ARPKD model) ex vivo | isoPPADS; AZ10606120 (P2X7) |
αβmeATP | Regulated [Ca2+]i | [63] | ||
| PCK rat (ARPKD model)/in vivo | P2rx7 knockout | P2rx7 knockout reduced cyst development through pannexin-1 channel and ATP accumulation in the cyst space, increased ENaC activity | [123] | |||
| P2X7 | ADPKD | Pkd2 morphant zebrafish/in vivo | A-438079; oxATP | Reduced cyst formation via ERK-dependent pathways | [144] | |
| Cultured human epithelial cells from ADPKD cysts/in vitro | oxATP | UTP; ATP; ADP |
Loss of flow-induced [Ca2+]i, reduced flow-sensitive ATP release; delayed and attenuated [Ca2+]i recovery was sensitive to oxATP | [121] | ||
|
Pkd1RC/RC mice (ADPKD)/in vivo M1 renal monolayers/in vitro |
αβmeATP | Pannexin-1 and P2X7 contributed to ATP release and decreased ENaC activity, promote cyst development | [122] | |||
| Metabotropic P2Y receptors | ||||||
| P2Ys | ADPKD | Human ADPKD epithelial primary cultures/in vitro | UTP UDP ADP |
Increased cytoplasmic [Ca2+]i, stimulated secretory Cl− transport | [140] | |
| MDCK-derived cysts (ADPKD)/in vitro | PPADS Suramin Reactive blue2 Apyrase |
Reduced cyst growth and slowed disease progression | [141] | |||
| P2Y1 | ADPKD | MDCK-derived cysts (ADPKD)/in vitro | PPADS Suramin Reactive blue2 MRS2179 (specific) |
Reduced cyst growth and slowed disease progression | [142] | |
Abbreviation: ENaC, epithelial Na+ channel.